Is MAP3K12 p.Ala671Asp (c.2012C>A) pathogenic?

MAP3K12 p.Ala671Asp (c.2012C>A) is classified Uncertain significance in MAP3K12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.1232); Absent from gnomAD v4.1.

How common is MAP3K12 p.Ala671Asp (c.2012C>A) in the general population?

MAP3K12 p.Ala671Asp (c.2012C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAP3K12 p.Ala671Asp (c.2012C>A)?

AlphaMissense predicts likely benign (score 0.1232) — an in-silico prediction, not a clinical call.

MAP3K12 p.Ala671Asp

c.2012C>A · VCV4103234

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1232 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1232	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -7.38	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 8.5	GERP 0.57, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 2,240 bp · p 0.77 · regional, not allelic
Overall
CADD	18.46	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A638D vs ClinVar A671D) — verify the residue.

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: MAP3K12
Protein: p.Ala671Asp
Coding: c.2012C>A
MANE Select: NM_001193511
Type: single nucleotide variant
Location: chr12:53482791 (GRCh38)
Gene constraint: LOEUF 0.247 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.80 · 12 PDB
Residue 671: the 'disordered' region

Full MAP3K12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP3K12 p.Gly661Arg Uncertain significance ★★ ⚠ same type
MAP3K12 p.Gly673Ser Benign ★★ same type
MAP3K12 p.Arg106Gln Uncertain significance ★ ⚠ same type
MAP3K12 p.Arg176Cys Uncertain significance ★ ⚠ same type
MAP3K12 p.Arg236Trp Uncertain significance ★ ⚠ same type
MAP3K12 p.Arg488Lys Uncertain significance ★ ⚠ same type
MAP3K12 p.Arg572Gln Uncertain significance ★ ⚠ same type
MAP3K12 p.Arg574His Uncertain significance ★ ⚠ same type

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/map3k12-p-ala671asp (accessed [today's date]).

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