Is F10 p.Ser374Pro (c.1120T>C) pathogenic?

F10 p.Ser374Pro (c.1120T>C) is classified Pathogenic in F10 (ClinVar, No assertion criteria, 1 submitter; last evaluated 1995-08-01). AlphaMissense: likely pathogenic (0.7349); Absent from gnomAD v4.1; Associated with factor X deficiency.

What condition is associated with F10 p.Ser374Pro (c.1120T>C)?

F10 p.Ser374Pro (c.1120T>C) is associated with factor X deficiency (ClinVar).

How common is F10 p.Ser374Pro (c.1120T>C) in the general population?

F10 p.Ser374Pro (c.1120T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F10 p.Ser374Pro (c.1120T>C)?

AlphaMissense predicts likely pathogenic (score 0.7349) — an in-silico prediction, not a clinical call.

F10 p.Ser374Pro

c.1120T>C · rs121964941 · VCV12060

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7349 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

factor X deficiency

Computational evidence

Protein change
AlphaMissense	0.7349	likely pathogenic ✓ concordant with ClinVar
REVEL	0.573	indeterminate
SaProt	LLR -14.38	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.88, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 10 kb · p 2.9e-09 · regional, not allelic
Overall
CADD	22.0	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.Ser374Pro
Coding: c.1120T>C
MANE Select: NM_000504
dbSNP: rs121964941
Type: single nucleotide variant
Location: chr13:113149170 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.47 · 192 PDB
Residue 374: the peptidase s1 domain; an α-helix; a UniProt-annotated variant site (in fa10d; marseille; decreased cleavage by factor ixa; normal catalytic efficiency for prothrombin)

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

Disease context

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

Similar variants

F10 p.Glu54Gly Likely pathogenic ★★ ⚠ same condition
F10 p.Gly21Arg Pathogenic ★★ ⚠ same condition
F10 p.Arg291Gln Uncertain significance ★★ ⚠ same condition
F10 p.Glu69Lys Likely pathogenic ★ ⚠ same condition
F10 p.Thr358Met Likely pathogenic ★ ⚠ same condition
F10 p.Arg27His Uncertain significance ★ ⚠ same condition
F10 p.Asp463His Uncertain significance ★ ⚠ same condition
F10 p.Cys277Ser 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-ser374pro (accessed [today's date]).

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