Is MAP3K10 p.Pro656Ala (c.1966C>G) pathogenic?

MAP3K10 p.Pro656Ala (c.1966C>G) is classified Uncertain significance in MAP3K10 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-08). AlphaMissense: likely benign (0.0512); Absent from gnomAD v4.1.

How common is MAP3K10 p.Pro656Ala (c.1966C>G) in the general population?

MAP3K10 p.Pro656Ala (c.1966C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAP3K10 p.Pro656Ala (c.1966C>G)?

AlphaMissense predicts likely benign (score 0.0512) — an in-silico prediction, not a clinical call.

MAP3K10 p.Pro656Ala

c.1966C>G · rs2514201251 · VCV2405625

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0512 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0512	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -6.93	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 1.2	GERP -1.7, phastCons 0.061
Regional constraint	o/e 1.01	unconstrained · MANE · 2,345 bp · p 0.89 · regional, not allelic
Overall
CADD	6.495	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.

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: MAP3K10
Protein: p.Pro656Ala
Coding: c.1966C>G
MANE Select: NM_002446
dbSNP: rs2514201251
Type: single nucleotide variant
Location: chr19:40213645 (GRCh38)
Gene constraint: LOEUF 0.506 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 61.33 · 1 PDB
Residue 656: the 'disordered' region

Full MAP3K10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP3K10 p.Pro656Leu Uncertain significance ★ ⚠ same residue
MAP3K10 p.Ala240Thr Uncertain significance ★ ⚠ same type
MAP3K10 p.Ala263Thr Uncertain significance ★ ⚠ same type
MAP3K10 p.Ala364Thr Uncertain significance ★ ⚠ same type
MAP3K10 p.Ala488Thr Uncertain significance ★ ⚠ same type
MAP3K10 p.Ala603Thr Uncertain significance ★ ⚠ same type
MAP3K10 p.Ala648Val Uncertain significance ★ ⚠ same type
MAP3K10 p.Ala658Thr 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/map3k10-p-pro656ala (accessed [today's date]).

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