Is F7 p.Phe313Leu (c.937T>C) pathogenic?

F7 p.Phe313Leu (c.937T>C) is classified Uncertain significance in F7 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely pathogenic (0.6043); Very rare (popmax 0.00223%, eas); Associated with factor VII deficiency.

What condition is associated with F7 p.Phe313Leu (c.937T>C)?

F7 p.Phe313Leu (c.937T>C) is associated with factor VII deficiency (ClinVar).

How common is F7 p.Phe313Leu (c.937T>C) in the general population?

F7 p.Phe313Leu (c.937T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about F7 p.Phe313Leu (c.937T>C)?

AlphaMissense predicts likely pathogenic (score 0.6043) — an in-silico prediction, not a clinical call.

F7 p.Phe313Leu

c.937T>C · rs762858015 · VCV311227

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6043 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

factor VII deficiency

Computational evidence

Protein change
AlphaMissense	0.6043	likely pathogenic
REVEL	0.218	benign-leaning
SaProt	LLR -4.95	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.46	GERP -3.1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	1.987	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F335L vs ClinVar F313L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,866 alleles

Overall 6.85e-05% 1/1,460,618 alleles · very rare

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.Phe313Leu
Coding: c.937T>C
MANE Select: NM_019616
dbSNP: rs762858015
Type: single nucleotide variant
Location: chr13:113118610 (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 313: 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 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
F7 p.Ala407Thr 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-phe313leu (accessed [today's date]).

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