Is PLVAP p.Ala331= (c.993C>T) pathogenic?

PLVAP p.Ala331= (c.993C>T) is classified Likely benign in PLVAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-18). Ultra-rare (popmax 0.0134%, eas).

How common is PLVAP p.Ala331= (c.993C>T) in the general population?

PLVAP p.Ala331= (c.993C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

PLVAP p.Ala331=

c.993C>T · VCV3698096

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

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 0.22	GERP -3.7, phastCons 0.8
Overall
CADD	8.209	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,894 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000806% 13/1,612,618 alleles · ultra-rare exomes 8/1,460,368 · genomes 5/152,250 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,482
African / African-American	0.00934%	10,707

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.Ala331=
Coding: c.993C>T
MANE Select: NM_031310
Type: single nucleotide variant
Location: chr19:17365472 (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.Ala331Ser Uncertain significance ★ ⚠ 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-ala331 (accessed [today's date]).

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