Is F7 p.Pro442fs (c.1325del) pathogenic?

F7 p.Pro442fs (c.1325del) is classified Pathogenic/Likely pathogenic in F7 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2025-08-15). Very rare (popmax 0.00822%, nfe); Associated with myocardial infarction, susceptibility to.

What condition is associated with F7 p.Pro442fs (c.1325del)?

F7 p.Pro442fs (c.1325del) is associated with myocardial infarction, susceptibility to, factor VII deficiency, congenital factor VII deficiency (ClinVar).

How common is F7 p.Pro442fs (c.1325del) in the general population?

F7 p.Pro442fs (c.1325del) is very rare (popmax 0.00822%, nfe) (gnomAD).

F7 p.Pro442fs

c.1325del · rs750457207 · VCV626999

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00822%, nfe)

Conditions

myocardial infarction, susceptibility to

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (8 of 8) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.6	GERP 0.35
Overall
CADD	19.12	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00822% European (non-Finnish) · 97/1,179,926 alleles

Filtering AF 0.00689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.00644% 103/1,599,880 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00822%	12,164
Remaining individualsnot grpmax-eligible	0.00801%	12,479
African / African-American	0.00133%	74,940

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.Pro442fs
Coding: c.1325del
MANE Select: NM_019616
dbSNP: rs750457207
Type: Deletion
Location: chr13:113118995 (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 442: an α-helix; the peptidase s1 domain

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

Disease context

myocardial infarction, susceptibility to — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: factor VII deficiency congenital factor VII deficiency

Similar variants

F7 p.Glu27fs Likely pathogenic ★ same condition
F7 p.Leu251_Asp255del Likely pathogenic ★ same condition
F7 p.Leu325fs Likely pathogenic ★ same condition
F7 p.Val291fs Likely pathogenic ★ same condition
F7 c.739+7_739+43del Conflicting classifications of pathogenicity ★ same condition
F7 p.Arg262fs Pathogenic same condition
F7 c.225+1G>C Pathogenic ★★ same condition
F7 c.364+1G>A 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-pro442fs (accessed [today's date]).

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