Is F12 p.Arg372Pro (c.1115G>C) pathogenic?

F12 p.Arg372Pro (c.1115G>C) is classified Pathogenic in F12 (ClinVar, No assertion criteria, 1 submitter; last evaluated 1994-08-15). AlphaMissense: likely pathogenic (0.7529); Very rare (popmax 0.00153%, nfe); Associated with FACTOR XII (LOCARNO).

What condition is associated with F12 p.Arg372Pro (c.1115G>C)?

F12 p.Arg372Pro (c.1115G>C) is associated with FACTOR XII (LOCARNO) (ClinVar).

How common is F12 p.Arg372Pro (c.1115G>C) in the general population?

F12 p.Arg372Pro (c.1115G>C) is very rare (popmax 0.00153%, nfe) (gnomAD).

What do computational predictors say about F12 p.Arg372Pro (c.1115G>C)?

AlphaMissense predicts likely pathogenic (score 0.7529) — an in-silico prediction, not a clinical call.

F12 p.Arg372Pro

c.1115G>C · rs118204454 · VCV1165

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7529 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

FACTOR XII (LOCARNO)

Computational evidence

Protein change
AlphaMissense	0.7529	likely pathogenic ✓ concordant with ClinVar
REVEL	0.536	indeterminate
SaProt	LLR -10.83	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.5	GERP 2.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 7,232 bp · p 0.39 · regional, not allelic
Overall
CADD	26.4	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 0.00153% European (non-Finnish) · 18/1,179,660 alleles

Filtering AF 0.000954% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00112% 18/1,602,802 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: F12
Protein: p.Arg372Pro
Coding: c.1115G>C
MANE Select: NM_003052 · reported on NM_000505
dbSNP: rs118204454
Type: single nucleotide variant
Location: chr5:177403994 (GRCh38)

Full F12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

FACTOR XII (LOCARNO)

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/f12-p-arg372pro (accessed [today's date]).

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