Is F12 p.Glu510Asp (c.1530G>C) pathogenic?

F12 p.Glu510Asp (c.1530G>C) is classified Uncertain significance in F12 (ClinVar, Single submitter, 1 submitter). AlphaMissense: ambiguous (0.3712); Absent from gnomAD v4.1; Associated with hereditary angioedema type 3.

What condition is associated with F12 p.Glu510Asp (c.1530G>C)?

F12 p.Glu510Asp (c.1530G>C) is associated with hereditary angioedema type 3 (ClinVar).

How common is F12 p.Glu510Asp (c.1530G>C) in the general population?

F12 p.Glu510Asp (c.1530G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F12 p.Glu510Asp (c.1530G>C)?

AlphaMissense predicts ambiguous (score 0.3712) — an in-silico prediction, not a clinical call.

F12 p.Glu510Asp

c.1530G>C · rs1763185944 · VCV983440

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3712 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary angioedema type 3

Computational evidence

Protein change
AlphaMissense	0.3712	ambiguous
REVEL	0.37	indeterminate
SaProt	LLR -9.13	tolerated
Splicing
SpliceAI	Δ0.28	donor loss, 27 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.38	GERP -3.9, phastCons 0.99
Regional constraint	o/e 0.97	unconstrained · MANE · 7,232 bp · p 0.39 · regional, not allelic
Overall
CADD	19.39	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: F12
Protein: p.Glu510Asp
Coding: c.1530G>C
MANE Select: NM_000505
dbSNP: rs1763185944
Type: single nucleotide variant
Location: chr5:177403255 (GRCh38)
Gene constraint: LOEUF 1.286 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.47 · 17 PDB
Residue 510: a disulfide bond; the peptidase s1 domain

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

Similar variants

F12 p.Thr328Lys Pathogenic ★★ ⚠ 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
F12 c.-4T>C Benign/Likely benign ★★ same condition
F12 c.-8C>T Likely benign ★★ same condition
F12 p.Ala207Pro 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-glu510asp (accessed [today's date]).

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