Is OVCA2 p.Val9Phe (c.25G>T) pathogenic?

OVCA2 p.Val9Phe (c.25G>T) is classified Uncertain significance in OVCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-31). AlphaMissense: ambiguous (0.3804); Ultra-rare (popmax 0.0129%, amr).

How common is OVCA2 p.Val9Phe (c.25G>T) in the general population?

OVCA2 p.Val9Phe (c.25G>T) is ultra-rare (popmax 0.0129%, amr) (gnomAD).

What do computational predictors say about OVCA2 p.Val9Phe (c.25G>T)?

AlphaMissense predicts ambiguous (score 0.3804) — an in-silico prediction, not a clinical call.

OVCA2 p.Val9Phe

c.25G>T · rs776753588 · VCV3207459

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3804 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0129%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.3804	ambiguous
REVEL	0.199	benign-leaning
SaProt	LLR -8.52	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.4	GERP 0.33, phastCons 0.74
Regional constraint	o/e 1.25	unconstrained · MANE · 1,053 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	19.34	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 0.0129% Admixed American · 7/54,468 alleles

Filtering AF 0.00602% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00422%

Overall 0.00128% 20/1,559,964 alleles · ultra-rare exomes 17/1,407,764 · genomes 3/152,200 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0129%	7,781
European (non-Finnish)	0.00112%	89,424

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: OVCA2
Protein: p.Val9Phe
Coding: c.25G>T
MANE Select: NM_080822
dbSNP: rs776753588
Type: single nucleotide variant
Location: chr17:2042072 (GRCh38)

Full OVCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/ovca2-p-val9phe (accessed [today's date]).

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