# NM_001031689.3(PLAA):c.1085_1086delinsAT (p.Val362Asp)

https://sugi.bio/variant/plaa-p-val362asp

## Summary

**PLAA p.Val362Asp (c.1085_1086delinsAT)** is classified **Uncertain significance** in PLAA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-20). No gnomAD frequency available for this variant.

**At a glance:** Uncertain significance · review: Single submitter · rsID rs2489191382 · 1 submitter · no gnomAD frequency available for this variant

## For patients & families {#patients}

This is a change in the PLAA gene that is currently of uncertain significance — a definitive interpretation has not yet been established, submitted by 1 submitter.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [PLAA](https://sugi.bio/atlas/gene/PLAA/) |
| Protein change (HGVS p.) | p.Val362Asp |
| Coding change (HGVS c.) | c.1085_1086delinsAT |
| MANE Select transcript | [NM_001031689](https://www.ncbi.nlm.nih.gov/nuccore/NM_001031689) |
| dbSNP | [rs2489191382](https://www.ncbi.nlm.nih.gov/snp/rs2489191382/) |
| Variant type | Indel |
| Location | chr9:26920338-26920339 (GRCh38) |
| ClinVar | [VCV1999833](https://www.ncbi.nlm.nih.gov/clinvar/variation/1999833/) |

**All HGVS expressions:** `NC_000009.11:g.26920336_26920337delinsAT`, `NC_000009.12:g.26920338_26920339delinsAT`, `NM_001031689.3:c.1085_1086delinsAT`, `NM_001321546.2:c.1085_1086delinsAT`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP -2.297, GERP -3.42 — fast-evolving / accelerated position
- Regional missense constraint: **o/e 0.95** across the covering region of the MANE Select transcript (26,905,514–26,947,045), spanning 41,531 bp. Chi-square p 0.094. Describes the region, not this allele; gnomAD v4.1.1's own constrained determination. *Descriptive; no ACMG code applied.*
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no indel variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.
- Population frequency: **no gnomAD frequency available for this variant** — rarity (ACMG PM2) and BA1/BS1 cannot be assessed for this variant.

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**PLAA** population constraint: LOEUF 0.678, pLI 0.0023759, missense-Z 0.69065. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 84.87, 58% of residues very-high.

**5 experimental structure(s)** (PDB): [2K89](https://www.rcsb.org/structure/2K89), [2K8A](https://www.rcsb.org/structure/2K8A), [2K8B](https://www.rcsb.org/structure/2K8B), [2K8C](https://www.rcsb.org/structure/2K8C), [3EBB](https://www.rcsb.org/structure/3EBB).

## What this gene does {#gene-function}

*Describes the biological roles of PLAA (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** PLAA's established molecular role includes phospholipase A2 activator activity.


### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** phospholipase A2 activator activity.

**Biological process:** macroautophagy, cellular response to lipopolysaccharide.

## Clinical significance {#significance}

**Uncertain significance** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2022-06-20.

**Submitter consensus:** unanimous (1/1 Uncertain significance).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Uncertain significance | criteria provided, single submitter | clinical testing | 2022-06-20 |

**Reported phenotype names (ClinVar):** not provided, none provided, RECLASSIFIED - ADRA2C POLYMORPHISM, RECLASSIFIED - ADRB1 POLYMORPHISM.

## Similar variants {#similar}

Related PLAA variant pages (same residue, condition, or type): [PLAA p.Val362=](/variant/plaa-p-val362), [PLAA p.Val362Ala](/variant/plaa-p-val362ala), [PLAA p.Pro653Ile](/variant/plaa-p-pro653ile), [PLAA p.Asn464Tyr](/variant/plaa-p-asn464tyr), [PLAA p.Ser11Thr](/variant/plaa-p-ser11thr).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-06); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-07-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 1999833). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*