Is F7 p.Val22Ile (c.64G>A) pathogenic?

F7 p.Val22Ile (c.64G>A) is classified Pathogenic/Likely pathogenic in F7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-12). AlphaMissense: likely benign (0.136); Very rare (popmax 0.0068%, eas); Associated with congenital factor VII deficiency.

What condition is associated with F7 p.Val22Ile (c.64G>A)?

F7 p.Val22Ile (c.64G>A) is associated with congenital factor VII deficiency, myocardial infarction, susceptibility to (ClinVar).

How common is F7 p.Val22Ile (c.64G>A) in the general population?

F7 p.Val22Ile (c.64G>A) is very rare (popmax 0.0068%, eas) (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.Val22Ile (c.64G>A)?

AlphaMissense predicts likely benign (score 0.136) — an in-silico prediction, not a clinical call.

F7 p.Val22Ile

c.64G>A · VCV3382510

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.136 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0068%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital factor VII deficiency

Computational evidence

Protein change
AlphaMissense	0.136	likely benign ⚠ discordant with ClinVar
REVEL	0.561	indeterminate
SaProt	LLR -6.01	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.62	donor loss · deltas
Constraint at this position
Conservation	phyloP 8.6	GERP 0.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	27.2	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 G22S vs ClinVar V22I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0068% East Asian · 3/44,104 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.000442% 7/1,585,266 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0068%	14,701
Remaining individualsnot grpmax-eligible	0.00325%	30,735
European (non-Finnish)	0.000171%	583,111

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.Val22Ile
Coding: c.64G>A
MANE Select: NM_019616
Type: single nucleotide variant
Location: chr13:113105905 (GRCh38)
Gene constraint: LOEUF 1.113 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.64 · 114 PDB

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

Also linked: myocardial infarction, susceptibility to

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.Gly22= Benign ★ 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-val22ile (accessed [today's date]).

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