Is F10 p.Pro383Ala (c.1147C>G) pathogenic?

F10 p.Pro383Ala (c.1147C>G) is classified Likely pathogenic in F10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely pathogenic (0.6752); Absent from gnomAD v4.1; Associated with congenital factor X deficiency.

What condition is associated with F10 p.Pro383Ala (c.1147C>G)?

F10 p.Pro383Ala (c.1147C>G) is associated with congenital factor X deficiency (ClinVar).

How common is F10 p.Pro383Ala (c.1147C>G) in the general population?

F10 p.Pro383Ala (c.1147C>G) is absent from gnomAD v4.1 (gnomAD).

How is Congenital factor X deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about F10 p.Pro383Ala (c.1147C>G)?

AlphaMissense predicts likely pathogenic (score 0.6752) — an in-silico prediction, not a clinical call.

F10 p.Pro383Ala

c.1147C>G · VCV4277962

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6752 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital factor X deficiency

Computational evidence

Protein change
AlphaMissense	0.6752	likely pathogenic ✓ concordant with ClinVar
REVEL	0.822	moderately pathogenic-leaning
SaProt	LLR -12.86	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 1.9, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 10 kb · p 2.9e-09 · regional, not allelic
Overall
CADD	26.2	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

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: F10
Protein: p.Pro383Ala
Coding: c.1147C>G
MANE Select: NM_000504
Type: single nucleotide variant
Location: chr13:113149197 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.47 · 192 PDB
Residue 383: the peptidase s1 domain; a β-strand; a UniProt-annotated variant site (in fa10d; friuli)

Full F10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital factor X deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital factor X deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

F10 p.Pro383Ser Pathogenic same residue
F10 p.Glu54Gly Likely pathogenic ★★ same condition
F10 p.Gly363Ser Likely pathogenic ★★ same condition
F10 p.Gly450Arg Likely pathogenic ★★ same condition
F10 p.Arg291Gln Uncertain significance ★★ ⚠ same condition
F10 p.Glu306Lys Uncertain significance ★★ ⚠ same condition
F10 p.Gly106= Uncertain significance ★★ same condition
F10 p.Gly154Arg Uncertain significance ★★ ⚠ 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/f10-p-pro383ala (accessed [today's date]).

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