Is F7 p.Val314Met (c.940G>A) pathogenic?

F7 p.Val314Met (c.940G>A) is classified Uncertain significance in F7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-25). AlphaMissense: likely benign (0.1602); Very rare (popmax 0.00446%, eas); Associated with factor VII deficiency.

What condition is associated with F7 p.Val314Met (c.940G>A)?

F7 p.Val314Met (c.940G>A) is associated with factor VII deficiency (ClinVar).

How common is F7 p.Val314Met (c.940G>A) in the general population?

F7 p.Val314Met (c.940G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about F7 p.Val314Met (c.940G>A)?

AlphaMissense predicts likely benign (score 0.1602) — an in-silico prediction, not a clinical call.

F7 p.Val314Met

c.940G>A · rs374305125 · VCV881853

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1602 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

factor VII deficiency

Computational evidence

Protein change
AlphaMissense	0.1602	likely benign
REVEL	0.271	benign-leaning
SaProt	LLR -1.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.72	GERP -1.5
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	16.35	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V336M vs ClinVar V314M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,876 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00192% 31/1,612,924 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,438
South Asian	0.0022%	45,534
European (non-Finnish)	0.00195%	51,303
Admixed American	0.00167%	60,014
Remaining individualsnot grpmax-eligible	0.0016%	62,494
Finnishnot grpmax-eligible	0.00159%	62,898
African / African-American	0.00133%	75,038

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: F7
Protein: p.Val314Met
Coding: c.940G>A
MANE Select: NM_019616
dbSNP: rs374305125
Type: single nucleotide variant
Location: chr13:113118613 (GRCh38)
Gene constraint: LOEUF 1.113 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.64 · 114 PDB
Residue 314: a UniProt-annotated variant site (in fa7d); an α-helix; a disulfide bond; the peptidase s1 domain

Full F7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

factor VII deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

F7 p.Val314Leu Uncertain significance ★ ⚠ same residue
F7 c.364+1G>A Pathogenic/Likely pathogenic ★★ same condition
F7 c.615+1G>T Pathogenic/Likely pathogenic ★★ same condition
F7 c.-30A>C Likely pathogenic ★★ same condition
F7 c.-55C>T Pathogenic/Likely pathogenic ★★ same condition
F7 c.-61T>G Likely pathogenic ★★ same condition
F7 p.Ala282Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
F7 p.Ala332Val Pathogenic/Likely pathogenic ★★ ⚠ same condition

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/f7-p-val314met (accessed [today's date]).

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