Is F12 p.Asp82Glu (c.246C>G) pathogenic?

F12 p.Asp82Glu (c.246C>G) is classified Uncertain significance in F12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely pathogenic (0.705); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with F12 p.Asp82Glu (c.246C>G)?

F12 p.Asp82Glu (c.246C>G) is associated with Inborn genetic diseases (ClinVar).

How common is F12 p.Asp82Glu (c.246C>G) in the general population?

F12 p.Asp82Glu (c.246C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F12 p.Asp82Glu (c.246C>G)?

AlphaMissense predicts likely pathogenic (score 0.705) — an in-silico prediction, not a clinical call.

F12 p.Asp82Glu

c.246C>G · VCV4619013

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.705 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.705	likely pathogenic
REVEL	0.432	indeterminate
SaProt	LLR -7.67	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP -0.24, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 7,232 bp · p 0.39 · regional, not allelic
Overall
CADD	21.3	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.Asp82Glu
Coding: c.246C>G
MANE Select: NM_000505
Type: single nucleotide variant
Location: chr5:177405775 (GRCh38)
Gene constraint: LOEUF 1.286 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.47 · 17 PDB
Residue 82: a disulfide bond; the fibronectin type-ii domain; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

F12 p.Ala452Thr Uncertain significance ★★ ⚠ same condition
F12 p.Arg55Trp Uncertain significance ★★ ⚠ same condition
F12 p.Glu288Lys Uncertain significance ★★ ⚠ same condition
F12 p.Gly360Val Uncertain significance ★★ ⚠ same condition
F12 p.Leu120His Uncertain significance ★★ ⚠ same condition
F12 p.Phe518Ser Uncertain significance ★★ ⚠ same condition
F12 p.Ser308Phe Uncertain significance ★★ ⚠ same condition
F12 p.Ser479Pro 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/f12-p-asp82glu (accessed [today's date]).

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