Is F7 p.Leu299Phe (c.895C>T) pathogenic?

F7 p.Leu299Phe (c.895C>T) is classified Likely pathogenic in F7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-22). AlphaMissense: likely pathogenic (0.5902); Very rare (popmax 0.0011%, sas); Associated with congenital factor VII deficiency.

What condition is associated with F7 p.Leu299Phe (c.895C>T)?

F7 p.Leu299Phe (c.895C>T) is associated with congenital factor VII deficiency (ClinVar).

How common is F7 p.Leu299Phe (c.895C>T) in the general population?

F7 p.Leu299Phe (c.895C>T) is very rare (popmax 0.0011%, 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.Leu299Phe (c.895C>T)?

AlphaMissense predicts likely pathogenic (score 0.5902) — an in-silico prediction, not a clinical call.

F7 p.Leu299Phe

c.895C>T · VCV3377703

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5902 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital factor VII deficiency

Computational evidence

Protein change
AlphaMissense	0.5902	likely pathogenic ✓ concordant with ClinVar
REVEL	0.615	indeterminate
SaProt	LLR -11.14	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 0.73	GERP -2.4, phastCons 0.16
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	23.1	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 L321F vs ClinVar L299F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,072 alleles

Overall 6.85e-05% 1/1,460,424 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.Leu299Phe
Coding: c.895C>T
MANE Select: NM_019616
Type: single nucleotide variant
Location: chr13:113118568 (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 299: 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

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

For Congenital factor VII deficiency (Orphanet):

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

Similar variants

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
F7 c.-61T>G 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-leu299phe (accessed [today's date]).

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