Is F7 p.Cys136Trp (c.408T>G) pathogenic?

F7 p.Cys136Trp (c.408T>G) is classified Uncertain significance in F7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-28). AlphaMissense: likely pathogenic (0.9596); Absent from gnomAD v4.1; Associated with factor VII deficiency.

What condition is associated with F7 p.Cys136Trp (c.408T>G)?

F7 p.Cys136Trp (c.408T>G) is associated with factor VII deficiency (ClinVar).

How common is F7 p.Cys136Trp (c.408T>G) in the general population?

F7 p.Cys136Trp (c.408T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F7 p.Cys136Trp (c.408T>G)?

AlphaMissense predicts likely pathogenic (score 0.9596) — an in-silico prediction, not a clinical call.

F7 p.Cys136Trp

c.408T>G · rs2142224651 · VCV1098446

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9596 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

factor VII deficiency

Computational evidence

Protein change
AlphaMissense	0.9596	likely pathogenic · top 7% in F7
REVEL	0.759	pathogenic-leaning
SaProt	LLR -14.66	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 -3.4	GERP -2.5
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM C158W vs ClinVar C136W) — 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.Cys136Trp
Coding: c.408T>G
MANE Select: NM_019616
dbSNP: rs2142224651
Type: single nucleotide variant
Location: chr13:113115703 (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 136: a β-strand; a disulfide bond; the egf-like 1; calcium-binding 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-cys136trp (accessed [today's date]).

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