Is F9 p.Ala37Val (c.110C>T) pathogenic?

F9 p.Ala37Val (c.110C>T) is classified Pathogenic in F9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 1997-07-01). AlphaMissense: ambiguous (0.4849); Very rare (popmax 0.000336%, nfe); Associated with Warfarin sensitivity, X-linked.

What condition is associated with F9 p.Ala37Val (c.110C>T)?

F9 p.Ala37Val (c.110C>T) is associated with Warfarin sensitivity, X-linked (ClinVar).

How common is F9 p.Ala37Val (c.110C>T) in the general population?

F9 p.Ala37Val (c.110C>T) is very rare (popmax 0.000336%, nfe) (gnomAD).

What do computational predictors say about F9 p.Ala37Val (c.110C>T)?

AlphaMissense predicts ambiguous (score 0.4849) — an in-silico prediction, not a clinical call.

F9 p.Ala37Val

c.110C>T · rs1327097914 · VCV10661

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4849 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000336%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Warfarin sensitivity, X-linked

Computational evidence

Protein change
AlphaMissense	0.4849	ambiguous
REVEL	0.936	strongly pathogenic-leaning
SaProt	LLR -9.98	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 5.2, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 6,280 bp · p 0.32 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000336% European (non-Finnish) · 3/893,244 alleles

Filtering AF 8.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000274% 3/1,093,773 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: F9
Protein: p.Ala37Val
Coding: c.110C>T
MANE Select: NM_000133
dbSNP: rs1327097914
Type: single nucleotide variant
Location: chrX:139537031 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB
Residue 37: an α-helix; a UniProt-annotated variant site (in warfs; reduced affinity of the glutamate carboxylase for the factor ix precursor; 4.4-fold decreased in the ec(50) for warfarin); a UniProt-annotated variant site (in warfs; 2.5-fold decreased in the ec(50) for warfarin)

Full F9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Warfarin sensitivity, X-linked — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

F9 p.Arg298Ter Pathogenic ★★ same condition
F9 p.Asn392Asp Pathogenic/Likely pathogenic ★★ ⚠ same condition
F9 p.Cys128Ter Pathogenic/Likely pathogenic ★★ same condition
F9 p.Ile443Thr Pathogenic/Likely pathogenic ★★ same condition
F9 c.*293C>T Uncertain significance ★★ same condition
F9 p.His303Tyr Benign/Likely benign ★★ same condition
F9 p.Ser220Thr Benign/Likely benign ★★ same condition
F9 c.520+13A>G Pathogenic ★★★ same type

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/f9-p-ala37val (accessed [today's date]).

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