Is F12 p.Arg310Ser (c.930G>C) pathogenic?

F12 p.Arg310Ser (c.930G>C) is classified Benign/Likely benign in F12 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-28). AlphaMissense: likely benign (0.094); Low-frequency (popmax 1.17%, afr); Associated with hereditary angioedema type 3.

What condition is associated with F12 p.Arg310Ser (c.930G>C)?

F12 p.Arg310Ser (c.930G>C) is associated with hereditary angioedema type 3, congenital factor XII deficiency (ClinVar).

How common is F12 p.Arg310Ser (c.930G>C) in the general population?

F12 p.Arg310Ser (c.930G>C) is low-frequency (popmax 1.17%, afr) (gnomAD).

What do computational predictors say about F12 p.Arg310Ser (c.930G>C)?

AlphaMissense predicts likely benign (score 0.094) — an in-silico prediction, not a clinical call.

F12 p.Arg310Ser

c.930G>C · rs77098327 · VCV352996

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.094 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.17%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary angioedema type 3

Computational evidence

Protein change
AlphaMissense	0.094	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -5.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.82	GERP -3
Regional constraint	o/e 0.97	unconstrained · MANE · 7,232 bp · p 0.39 · regional, not allelic
Overall
CADD	5.97	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 1.17% African / African-American · 871/74,728 alleles

Filtering AF 1.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.08%

Overall 0.0625% 1,000/1,600,816 alleles · low-frequency exomes 491/1,448,488 · genomes 509/152,328 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.17%	86
Admixed American	0.104%	962
Remaining individualsnot grpmax-eligible	0.0906%	1,104
Middle Eastern	0.0501%	1,995
South Asian	0.00223%	44,769
European (non-Finnish)	0.000597%	167,620

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.Arg310Ser
Coding: c.930G>C
MANE Select: NM_000505
dbSNP: rs77098327
Type: single nucleotide variant
Location: chr5:177404284 (GRCh38)
Gene constraint: LOEUF 1.286 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.47 · 17 PDB
Residue 310: the 'disordered' region

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

Disease context

hereditary angioedema type 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital factor XII deficiency

Similar variants

F12 p.Arg310Trp Uncertain significance ★ ⚠ same residue
F12 p.Thr328Lys Pathogenic ★★ ⚠ same condition
F12 p.Gly360Val Uncertain significance ★★ ⚠ same condition
F12 p.Leu120His Uncertain significance ★★ ⚠ same condition
F12 c.1019-28T>C Benign ★★ same condition
F12 c.1251-9C>T Benign/Likely benign ★★ same condition
F12 c.1681-7G>A Benign/Likely benign ★★ same condition
F12 c.398-12C>T Benign/Likely benign ★★ 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/f12-p-arg310ser (accessed [today's date]).

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