Is F7 p.Phe306Ser (c.917T>C) pathogenic?

F7 p.Phe306Ser (c.917T>C) is classified Pathogenic in F7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 1996-11-29). AlphaMissense: likely pathogenic (0.8273); Absent from gnomAD v4.1; Associated with factor VII deficiency.

What condition is associated with F7 p.Phe306Ser (c.917T>C)?

F7 p.Phe306Ser (c.917T>C) is associated with factor VII deficiency (ClinVar).

How common is F7 p.Phe306Ser (c.917T>C) in the general population?

F7 p.Phe306Ser (c.917T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F7 p.Phe306Ser (c.917T>C)?

AlphaMissense predicts likely pathogenic (score 0.8273) — an in-silico prediction, not a clinical call.

F7 p.Phe306Ser

c.917T>C · rs387906508 · VCV12090

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8273 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

factor VII deficiency

Computational evidence

Protein change
AlphaMissense	0.8273	likely pathogenic ✓ concordant with ClinVar
REVEL	0.541	indeterminate
SaProt	LLR -14.21	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	24.4	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 F328S vs ClinVar F306S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: F7
Protein: p.Phe306Ser
Coding: c.917T>C
MANE Select: NM_019616
dbSNP: rs387906508
Type: single nucleotide variant
Location: chr13:113118590 (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 306: a β-strand; 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-phe306ser (accessed [today's date]).

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