Is ERVV-2 p.Val347Ile (c.1039G>A) pathogenic?

ERVV-2 p.Val347Ile (c.1039G>A) is classified Uncertain significance in ERVV-2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely benign (0.0977); Ultra-rare (popmax 0.0606%, amr).

How common is ERVV-2 p.Val347Ile (c.1039G>A) in the general population?

ERVV-2 p.Val347Ile (c.1039G>A) is ultra-rare (popmax 0.0606%, amr) (gnomAD).

What do computational predictors say about ERVV-2 p.Val347Ile (c.1039G>A)?

AlphaMissense predicts likely benign (score 0.0977) — an in-silico prediction, not a clinical call.

ERVV-2 p.Val347Ile

c.1039G>A · rs957273513 · VCV2357260

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0977 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0606%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.0977	likely benign
SaProt	LLR -6.51	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 -1.1	GERP -0.39
Regional constraint	o/e 1.26	unconstrained · MANE · 600 bp · p 0.00074 · regional, not allelic
Overall
CADD	0.53	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 0.0606% Admixed American · 30/49,538 alleles

Filtering AF 0.0436% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0378%

Overall 0.0271% 197/727,502 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0606%	1,651
European (non-Finnish)	0.0386%	2,592
Middle Eastern	0.0226%	4,432
Remaining individualsnot grpmax-eligible	0.0209%	4,783
African / African-American	0.00175%	57,018

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-2
Protein: p.Val347Ile
Coding: c.1039G>A
MANE Select: NM_001191055
dbSNP: rs957273513
Type: single nucleotide variant
Location: chr19:53050290 (GRCh38)
Gene constraint: LOEUF 1.451 · pLI 0.37 (gnomAD)
Structure: AlphaFold pLDDT 46.18

Full ERVV-2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERVV-2 p.Ala337Thr Uncertain significance ★ ⚠ same type
ERVV-2 p.Ala442Ser Uncertain significance ★ ⚠ same type
ERVV-2 p.Ala450Thr Uncertain significance ★ ⚠ same type
ERVV-2 p.Arg195Ser Uncertain significance ★ ⚠ same type
ERVV-2 p.Arg304Gln Uncertain significance ★ ⚠ same type
ERVV-2 p.Arg304Gly Uncertain significance ★ ⚠ same type
ERVV-2 p.Arg441Gly Uncertain significance ★ ⚠ same type
ERVV-2 p.Arg441Lys 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-2-p-val347ile (accessed [today's date]).

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