Is MAP3K10 p.Ala648Val (c.1943C>T) pathogenic?

MAP3K10 p.Ala648Val (c.1943C>T) is classified Uncertain significance in MAP3K10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). AlphaMissense: likely benign (0.0778); Very rare (popmax 0.00937%, sas).

How common is MAP3K10 p.Ala648Val (c.1943C>T) in the general population?

MAP3K10 p.Ala648Val (c.1943C>T) is very rare (popmax 0.00937%, sas) (gnomAD).

What do computational predictors say about MAP3K10 p.Ala648Val (c.1943C>T)?

AlphaMissense predicts likely benign (score 0.0778) — an in-silico prediction, not a clinical call.

MAP3K10 p.Ala648Val

c.1943C>T · VCV3542751

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0778 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00937%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0778	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -7.96	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 -0.12	GERP -0.63, phastCons 0.71
Regional constraint	o/e 1.01	unconstrained · MANE · 2,345 bp · p 0.89 · regional, not allelic
Overall
CADD	13.67	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

Grpmax group 0.00937% South Asian · 8/85,372 alleles

Filtering AF 0.00462% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0034%

Overall 0.00117% 18/1,537,764 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00937%	10,672
Admixed American	0.00408%	24,506
Remaining individualsnot grpmax-eligible	0.00171%	58,534
European (non-Finnish)	0.000611%	163,675

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: MAP3K10
Protein: p.Ala648Val
Coding: c.1943C>T
MANE Select: NM_002446
Type: single nucleotide variant
Location: chr19:40213622 (GRCh38)
Gene constraint: LOEUF 0.506 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 61.33 · 1 PDB
Residue 648: the 'disordered' region

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

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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-ala648val (accessed [today's date]).

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