Is ERVV-1 p.Ala331Val (c.992C>T) pathogenic?

ERVV-1 p.Ala331Val (c.992C>T) is classified Uncertain significance in ERVV-1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely benign (0.1844); Ultra-rare (popmax 0.0308%, eas).

How common is ERVV-1 p.Ala331Val (c.992C>T) in the general population?

ERVV-1 p.Ala331Val (c.992C>T) is ultra-rare (popmax 0.0308%, eas) (gnomAD).

What do computational predictors say about ERVV-1 p.Ala331Val (c.992C>T)?

AlphaMissense predicts likely benign (score 0.1844) — an in-silico prediction, not a clinical call.

ERVV-1 p.Ala331Val

c.992C>T · rs922567011 · VCV3090393

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1844 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0308%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.1844	likely benign
SaProt	LLR -7.42	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.4	GERP 0.19
Regional constraint	o/e 0.21	constrained · MANE · 302 bp · p 3.2e-19 · regional, not allelic
Overall
CADD	7.51	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 0.0308% East Asian · 12/39,010 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0139%

Overall 0.00192% 24/1,248,538 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0308%	3,251
Remaining individualsnot grpmax-eligible	0.00596%	16,767
Admixed American	0.00199%	50,178
European (non-Finnish)	0.000901%	110,987

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: ERVV-1
Protein: p.Ala331Val
Coding: c.992C>T
MANE Select: NM_152473
dbSNP: rs922567011
Type: single nucleotide variant
Location: chr19:53015082 (GRCh38)
Structure: AlphaFold pLDDT 42.29

Full ERVV-1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERVV-1 p.Ala337Ser Uncertain significance ★ ⚠ same type
ERVV-1 p.Ala337Thr Uncertain significance ★ ⚠ same type
ERVV-1 p.Ala372Val Uncertain significance ★ ⚠ same type
ERVV-1 p.Arg175Gln Uncertain significance ★ ⚠ same type
ERVV-1 p.Arg195Ser Uncertain significance ★ ⚠ same type
ERVV-1 p.Arg246Gln Uncertain significance ★ ⚠ same type
ERVV-1 p.Arg304Gln Uncertain significance ★ ⚠ same type
ERVV-1 p.Arg304Leu 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/ervv-1-p-ala331val (accessed [today's date]).

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