Is MAP3K10 p.Arg421Gln (c.1262G>A) pathogenic?

MAP3K10 p.Arg421Gln (c.1262G>A) is classified Uncertain significance in MAP3K10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-09). AlphaMissense: likely benign (0.0876); Very rare (popmax 0.00668%, afr).

How common is MAP3K10 p.Arg421Gln (c.1262G>A) in the general population?

MAP3K10 p.Arg421Gln (c.1262G>A) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about MAP3K10 p.Arg421Gln (c.1262G>A)?

AlphaMissense predicts likely benign (score 0.0876) — an in-silico prediction, not a clinical call.

MAP3K10 p.Arg421Gln

c.1262G>A · VCV4103184

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0876 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0876	likely benign
REVEL	0.298	indeterminate
SaProt	LLR -8.85	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 21 kb · p 9.4e-15 · regional, not allelic
Overall
CADD	27.9	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 0.00668% African / African-American · 5/74,876 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00124% 20/1,610,728 alleles · very rare exomes 18/1,458,552 · genomes 2/152,176 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,975
East Asian	0.00224%	44,728
Finnishnot grpmax-eligible	0.00157%	63,608
South Asian	0.0011%	90,628
European (non-Finnish)	0.00102%	98,203

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.Arg421Gln
Coding: c.1262G>A
MANE Select: NM_002446
Type: single nucleotide variant
Location: chr19:40205984 (GRCh38)
Gene constraint: LOEUF 0.506 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 61.33 · 1 PDB
Residue 421: the 'leucine-zipper 2' 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-arg421gln (accessed [today's date]).

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