Is ERVV-2 p.Pro338Leu (c.1013C>T) pathogenic?

ERVV-2 p.Pro338Leu (c.1013C>T) is classified Uncertain significance in ERVV-2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). AlphaMissense: ambiguous (0.5608); Rare (popmax 0.428%, afr).

How common is ERVV-2 p.Pro338Leu (c.1013C>T) in the general population?

ERVV-2 p.Pro338Leu (c.1013C>T) is rare (popmax 0.428%, afr) (gnomAD).

What do computational predictors say about ERVV-2 p.Pro338Leu (c.1013C>T)?

AlphaMissense predicts ambiguous (score 0.5608) — an in-silico prediction, not a clinical call.

ERVV-2 p.Pro338Leu

c.1013C>T · rs1419812165 · VCV2393370

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5608 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.428%, afr)

Computational evidence

Protein change
AlphaMissense	0.5608	ambiguous
SaProt	LLR -7.10	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.89	GERP 0.19, phastCons 0.002
Regional constraint	o/e 1.26	unconstrained · MANE · 600 bp · p 0.00074 · regional, not allelic
Overall
CADD	16.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.428% African / African-American · 224/52,300 alleles

Filtering AF 0.382% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.364%

Overall 0.0304% 241/791,920 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.428%	233
Admixed American	0.0204%	4,898
Remaining individualsnot grpmax-eligible	0.00846%	11,817
South Asian	0.00146%	68,472
European (non-Finnish)	0.00063%	158,647

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.Pro338Leu
Coding: c.1013C>T
MANE Select: NM_001191055
dbSNP: rs1419812165
Type: single nucleotide variant
Location: chr19:53050264 (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-pro338leu (accessed [today's date]).

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