Is F11 p.His145Pro (c.434A>C) pathogenic?

F11 p.His145Pro (c.434A>C) is classified Likely pathogenic in F11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-29). AlphaMissense: likely benign (0.2661); Absent from gnomAD v4.1; Associated with congenital factor XI deficiency.

What condition is associated with F11 p.His145Pro (c.434A>C)?

F11 p.His145Pro (c.434A>C) is associated with congenital factor XI deficiency (ClinVar).

How common is F11 p.His145Pro (c.434A>C) in the general population?

F11 p.His145Pro (c.434A>C) is absent from gnomAD v4.1 (gnomAD).

How is Congenital factor XI deficiency inherited?

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

What do computational predictors say about F11 p.His145Pro (c.434A>C)?

AlphaMissense predicts likely benign (score 0.2661) — an in-silico prediction, not a clinical call.

F11 p.His145Pro

c.434A>C · rs199657604 · VCV3065582

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2661 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital factor XI deficiency

Computational evidence

Protein change
AlphaMissense	0.2661	likely benign ⚠ discordant with ClinVar
REVEL	0.689	pathogenic-leaning
SaProt	LLR -10.28	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 2.4, phastCons 1
Overall
CADD	22.6	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: F11
Protein: p.His145Pro
Coding: c.434A>C
MANE Select: NM_000128
dbSNP: rs199657604
Type: single nucleotide variant
Location: chr4:186274224 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 145: a β-strand; a disulfide bond; the apple 2 domain

Full F11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Congenital factor XI deficiency (Orphanet):

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

Similar variants

F11 p.His145Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
F11 p.His145= Likely benign ★ same residue
F11 c.1481-1G>T Likely pathogenic ★★ same condition
F11 c.1716+1G>A Pathogenic ★★ same condition
F11 c.325+1G>A Pathogenic ★★ same condition
F11 c.326-1G>A Pathogenic ★★ same condition
F11 c.755+2T>C Pathogenic ★★ same condition
F11 c.865+2T>C 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/f11-p-his145pro (accessed [today's date]).

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