Is F3 p.Val25Phe (c.73G>T) pathogenic?

F3 p.Val25Phe (c.73G>T) is classified Uncertain significance in F3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: likely benign (0.1342); Very rare (popmax 0.0065%, amr).

How common is F3 p.Val25Phe (c.73G>T) in the general population?

F3 p.Val25Phe (c.73G>T) is very rare (popmax 0.0065%, amr) (gnomAD).

What do computational predictors say about F3 p.Val25Phe (c.73G>T)?

AlphaMissense predicts likely benign (score 0.1342) — an in-silico prediction, not a clinical call.

F3 p.Val25Phe

c.73G>T · VCV3847024

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1342 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0065%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1342	likely benign
REVEL	0.299	indeterminate
SaProt	LLR -6.97	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.053	GERP -0.85, phastCons 0.27
Regional constraint	o/e 0.97	unconstrained · MANE · 11 kb · p 0.63 · regional, not allelic
Overall
CADD	17.06	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 0.0065% Admixed American · 3/46,146 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000878%

Overall 0.000399% 6/1,505,004 alleles · very rare exomes 4/1,352,806 · genomes 2/152,198 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0065%	15,382
European (non-Finnish)	0.000266%	375,801

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: F3
Protein: p.Val25Phe
Coding: c.73G>T
MANE Select: NM_001993
Type: single nucleotide variant
Location: chr1:94541564 (GRCh38)
Gene constraint: LOEUF 0.839 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.40 · 54 PDB

Full F3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

F3 p.Arg163Trp Benign ★★ ⚠ same type
F3 p.Gly281Glu Benign ★★ same type
F3 p.Thr36Ala Benign ★★ same type
F3 p.Ala17Thr Uncertain significance ★ ⚠ same type
F3 p.Ala30Thr Uncertain significance ★ ⚠ same type
F3 p.Arg11His Uncertain significance ★ ⚠ same type
F3 p.Arg176Trp Uncertain significance ★ same type
F3 p.Arg228Gln 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/f3-p-val25phe (accessed [today's date]).

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