Is ERVV-1 p.Pro207Ser (c.619C>T) pathogenic?

ERVV-1 p.Pro207Ser (c.619C>T) is classified Uncertain significance in ERVV-1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.1123); Very rare (popmax 0.00593%, nfe).

How common is ERVV-1 p.Pro207Ser (c.619C>T) in the general population?

ERVV-1 p.Pro207Ser (c.619C>T) is very rare (popmax 0.00593%, nfe) (gnomAD).

What do computational predictors say about ERVV-1 p.Pro207Ser (c.619C>T)?

AlphaMissense predicts likely benign (score 0.1123) — an in-silico prediction, not a clinical call.

ERVV-1 p.Pro207Ser

c.619C>T · VCV4250988

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1123 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00593%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.1123	likely benign
SaProt	LLR -6.14	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 -0.05	GERP 0.18
Regional constraint	o/e 0.39	unconstrained · MANE · 78 bp · p 0.00072 · regional, not allelic
Overall
CADD	1.441	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 0.00593% European (non-Finnish) · 68/1,146,704 alleles

Filtering AF 0.00475% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00435%

Overall 0.0047% 72/1,531,114 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00593%	16,863
Remaining individualsnot grpmax-eligible	0.00334%	29,957
African / African-American	0.00291%	34,330

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.Pro207Ser
Coding: c.619C>T
MANE Select: NM_152473
Type: single nucleotide variant
Location: chr19:53014709 (GRCh38)
Structure: AlphaFold pLDDT 42.29

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

Similar variants

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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

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-pro207ser (accessed [today's date]).

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