Is PLAA p.Pro653Ile (c.1957_1958delinsAT) pathogenic?

PLAA p.Pro653Ile (c.19571958delinsAT) is classified Uncertain significance in PLAA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-02-17). No gnomAD frequency available for this variant; Associated with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies.

How common is PLAA p.Pro653Ile (c.1957_1958delinsAT) in the general population?

PLAA p.Pro653Ile (c.1957_1958delinsAT) is no gnomAD frequency available for this variant (gnomAD).

PLAA p.Pro653Ile

Q: What condition is associated with PLAA p.Pro653Ile (c.1957_1958delinsAT)?

PLAA p.Pro653Ile (c.1957_1958delinsAT) is associated with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies (ClinVar).

c.1957_1958delinsAT · rs2489157116 · VCV2013465

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 42 kb · p 0.094 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PLAA
Protein: p.Pro653Ile
Coding: c.1957_1958delinsAT
MANE Select: NM_001031689
dbSNP: rs2489157116
Type: Indel
Location: chr9:26905941 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.87 · 5 PDB
Residue 653: an α-helix; the pul domain

Full PLAA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PLAA p.Arg524Ter Likely pathogenic ★★ same condition
PLAA p.Ala264Thr Uncertain significance ★★ ⚠ same condition
PLAA p.Gly457Ala Uncertain significance ★★ ⚠ same condition
PLAA p.Ile356Met Uncertain significance ★★ same condition
PLAA p.Pro161Ser Uncertain significance ★★ ⚠ same condition
PLAA p.Thr114Ala Uncertain significance ★★ ⚠ same condition
PLAA p.Thr304Arg Uncertain significance ★★ ⚠ same condition
PLAA p.Tyr775His Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/plaa-p-pro653ile (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown