Is F7 p.Ser149Pro (c.445T>C) pathogenic?

F7 p.Ser149Pro (c.445T>C) is classified Uncertain significance in F7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-11-24). AlphaMissense: ambiguous (0.4212); Absent from gnomAD v4.1; Associated with congenital factor VII deficiency.

What condition is associated with F7 p.Ser149Pro (c.445T>C)?

F7 p.Ser149Pro (c.445T>C) is associated with congenital factor VII deficiency (ClinVar).

How common is F7 p.Ser149Pro (c.445T>C) in the general population?

F7 p.Ser149Pro (c.445T>C) is absent from gnomAD v4.1 (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.Ser149Pro (c.445T>C)?

AlphaMissense predicts ambiguous (score 0.4212) — an in-silico prediction, not a clinical call.

F7 p.Ser149Pro

c.445T>C · rs755048394 · VCV2664036

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4212 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

congenital factor VII deficiency

Computational evidence

Protein change
AlphaMissense	0.4212	ambiguous
REVEL	0.458	indeterminate
SaProt	LLR -11.28	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1	GERP -0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	14.43	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 S171P vs ClinVar S149P) — 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.Ser149Pro
Coding: c.445T>C
MANE Select: NM_019616
dbSNP: rs755048394
Type: single nucleotide variant
Location: chr13:113115740 (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 149: a β-strand; the egf-like 2 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-ser149pro (accessed [today's date]).

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