Is F7 p.Cys348Phe (c.1043G>T) pathogenic?

F7 p.Cys348Phe (c.1043G>T) is classified Pathogenic/Likely pathogenic in F7 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2024-05-20). AlphaMissense: likely pathogenic (0.9455); Ultra-rare (popmax 0.0373%, sas); Associated with congenital factor VII deficiency.

What condition is associated with F7 p.Cys348Phe (c.1043G>T)?

F7 p.Cys348Phe (c.1043G>T) is associated with congenital factor VII deficiency, factor VII deficiency, myocardial infarction, susceptibility to (ClinVar).

How common is F7 p.Cys348Phe (c.1043G>T) in the general population?

F7 p.Cys348Phe (c.1043G>T) is ultra-rare (popmax 0.0373%, sas) (gnomAD).

How is Congenital factor VII deficiency inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about F7 p.Cys348Phe (c.1043G>T)?

AlphaMissense predicts likely pathogenic (score 0.9455) — an in-silico prediction, not a clinical call.

F7 p.Cys348Phe

c.1043G>T · rs121964927 · VCV265135

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely pathogenic

0.9455 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0373%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital factor VII deficiency

Computational evidence

Protein change
AlphaMissense	0.9455	likely pathogenic ✓ concordant with ClinVar · top 8% in F7
REVEL	0.886	moderately pathogenic-leaning
SaProt	LLR -14.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	29.2	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 C370F vs ClinVar C348F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0373% South Asian · 34/91,068 alleles

Filtering AF 0.0274% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.024%

Overall 0.00366% 59/1,613,040 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0373%	2,678
Middle Eastern	0.033%	3,031
European (non-Finnish)	0.00178%	56,189
Remaining individualsnot grpmax-eligible	0.0016%	62,482
African / African-American	0.00133%	75,050

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.Cys348Phe
Coding: c.1043G>T
MANE Select: NM_019616
dbSNP: rs121964927
Type: single nucleotide variant
Location: chr13:113118716 (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 348: a β-strand; the peptidase s1 domain

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

Disease context

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

Also linked: factor VII deficiency myocardial infarction, susceptibility to

For Congenital factor VII deficiency (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

F7 p.Cys348Tyr Likely pathogenic ★★ same residue
F7 c.225+1G>C Pathogenic ★★ same condition
F7 c.364+1G>A Pathogenic/Likely pathogenic ★★ same condition
F7 c.505+78G>A Pathogenic/Likely pathogenic ★★ same condition
F7 c.615+1G>T Pathogenic/Likely pathogenic ★★ same condition
F7 c.739+1G>A Pathogenic/Likely pathogenic ★★ same condition
F7 c.-30A>C Likely pathogenic ★★ same condition
F7 c.-55C>T 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-cys348phe (accessed [today's date]).

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