Is PLVAP p.Ala331Ser (c.991G>T) pathogenic?

PLVAP p.Ala331Ser (c.991G>T) is classified Uncertain significance in PLVAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-29). AlphaMissense: likely benign (0.1022); Very rare (popmax 6.2e-05%).

How common is PLVAP p.Ala331Ser (c.991G>T) in the general population?

PLVAP p.Ala331Ser (c.991G>T) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about PLVAP p.Ala331Ser (c.991G>T)?

AlphaMissense predicts likely benign (score 0.1022) — an in-silico prediction, not a clinical call.

PLVAP p.Ala331Ser

c.991G>T · VCV3664852

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1022 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1022	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 25 kb · p 0.43 · regional, not allelic
Overall
CADD	15.62	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,612,672 alleles · very rare exomes 1/1,460,302 · genomes 0/152,370 · joint denominator

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: PLVAP
Protein: p.Ala331Ser
Coding: c.991G>T
MANE Select: NM_031310
Type: single nucleotide variant
Location: chr19:17365474 (GRCh38)
Gene constraint: LOEUF 1.015 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.39
Residue 331: a UniProt-annotated variant site (in diar10)

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

Similar variants

PLVAP p.Ala331= Likely benign ★ same residue
PLVAP p.Arg358Ter Pathogenic ★★ same type
PLVAP p.Ala292Val Uncertain significance ★★ ⚠ same type
PLVAP p.Ala385Thr Uncertain significance ★★ ⚠ same type
PLVAP p.Ala94Thr Uncertain significance ★★ ⚠ same type
PLVAP p.Arg13Trp Uncertain significance ★★ ⚠ same type
PLVAP p.Arg211Cys Uncertain significance ★★ ⚠ same type
PLVAP p.Arg238His 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/plvap-p-ala331ser (accessed [today's date]).

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