Is F7 p.Ala229Val (c.686C>T) pathogenic?

F7 p.Ala229Val (c.686C>T) is classified Conflicting classifications of pathogenicity in F7 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-06-21). AlphaMissense: likely pathogenic (0.8531); Very rare (popmax 0.00329%, sas); Associated with congenital factor VII deficiency.

What condition is associated with F7 p.Ala229Val (c.686C>T)?

F7 p.Ala229Val (c.686C>T) is associated with congenital factor VII deficiency (ClinVar).

How common is F7 p.Ala229Val (c.686C>T) in the general population?

F7 p.Ala229Val (c.686C>T) is very rare (popmax 0.00329%, 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.Ala229Val (c.686C>T)?

AlphaMissense predicts likely pathogenic (score 0.8531) — an in-silico prediction, not a clinical call.

F7 p.Ala229Val

c.686C>T · rs747989049 · VCV1706362

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8531 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital factor VII deficiency

Computational evidence

Protein change
AlphaMissense	0.8531	likely pathogenic
REVEL	0.849	moderately pathogenic-leaning
SaProt	LLR -12.60	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 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	25.7	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 A251V vs ClinVar A229V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,078 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00136% 22/1,614,052 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,359
Remaining individualsnot grpmax-eligible	0.0032%	31,240
European (non-Finnish)	0.00136%	73,752
African / African-American	0.00133%	74,928

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.Ala229Val
Coding: c.686C>T
MANE Select: NM_019616
dbSNP: rs747989049
Type: single nucleotide variant
Location: chr13:113117543 (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 229: 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 p.Ala229Thr Conflicting classifications of pathogenicity ★ ⚠ 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-ala229val (accessed [today's date]).

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