Is PLAA p.Val362= (c.1086C>T) pathogenic?

PLAA p.Val362= (c.1086C>T) is classified Likely benign in PLAA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-04). Ultra-rare (popmax 0.0758%, sas).

How common is PLAA p.Val362= (c.1086C>T) in the general population?

PLAA p.Val362= (c.1086C>T) is ultra-rare (popmax 0.0758%, sas) (gnomAD).

PLAA p.Val362=

c.1086C>T · rs749838482 · VCV2182733

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0758%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.3	GERP -3.4
Overall
CADD	5.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0758% South Asian · 69/91,038 alleles

Filtering AF 0.0613% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0561%

Overall 0.00589% 86/1,461,048 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0758%	1,319
Remaining individualsnot grpmax-eligible	0.0032%	31,240
European (non-Finnish)	0.00127%	78,622

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PLAA
Protein: p.Val362=
Coding: c.1086C>T
MANE Select: NM_001031689
dbSNP: rs749838482
Type: single nucleotide variant
Location: chr9:26920338 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.87 · 5 PDB

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

Similar variants

PLAA p.Val362Ala Uncertain significance ★ same residue
PLAA p.Val362Asp Uncertain significance ★ same residue
PLAA p.Arg524Ter Likely pathogenic ★★ same type
PLAA p.Ala156Val Uncertain significance ★★ ⚠ same type
PLAA p.Ala264Thr Uncertain significance ★★ ⚠ same type
PLAA p.Ala271Val Uncertain significance ★★ ⚠ same type
PLAA p.Arg268Gln Uncertain significance ★★ ⚠ same type
PLAA p.Arg373Thr Uncertain significance ★★ ⚠ same type

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-val362 (accessed [today's date]).

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