Is ERVV-2 p.Asn403Ser (c.1208A>G) pathogenic?

ERVV-2 p.Asn403Ser (c.1208A>G) is classified Uncertain significance in ERVV-2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-13). AlphaMissense: likely benign (0.1511); Rare (popmax 0.169%, eas).

How common is ERVV-2 p.Asn403Ser (c.1208A>G) in the general population?

ERVV-2 p.Asn403Ser (c.1208A>G) is rare (popmax 0.169%, eas) (gnomAD).

What do computational predictors say about ERVV-2 p.Asn403Ser (c.1208A>G)?

AlphaMissense predicts likely benign (score 0.1511) — an in-silico prediction, not a clinical call.

ERVV-2 p.Asn403Ser

c.1208A>G · rs377417317 · VCV2246685

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1511 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.169%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.1511	likely benign
SaProt	LLR -8.95	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 0.25	GERP 0.2, phastCons 0.001
Regional constraint	o/e 1.26	unconstrained · MANE · 600 bp · p 0.00074 · regional, not allelic
Overall
CADD	8.242	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 0.169% East Asian · 63/37,362 alleles

Filtering AF 0.135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.123%

Overall 0.0652% 472/723,978 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.169%	593
South Asian	0.103%	971
Admixed American	0.072%	1,390
European (non-Finnish)	0.0663%	1,508
Remaining individualsnot grpmax-eligible	0.0569%	1,758
Middle Eastern	0.0226%	4,418
African / African-American	0.0208%	4,815
Finnishnot grpmax-eligible	0.00452%	22,126
Ashkenazi Jewishnot grpmax-eligible	0.00423%	23,628

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.Asn403Ser
Coding: c.1208A>G
MANE Select: NM_001191055
dbSNP: rs377417317
Type: single nucleotide variant
Location: chr19:53050459 (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-asn403ser (accessed [today's date]).

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