Is MAPK10 p.His36Arg (c.107A>G) pathogenic?

MAPK10 p.His36Arg (c.107A>G) is classified Uncertain significance in MAPK10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-02). AlphaMissense: likely benign (0.0922); Very rare (popmax 0.00668%, amr).

How common is MAPK10 p.His36Arg (c.107A>G) in the general population?

MAPK10 p.His36Arg (c.107A>G) is very rare (popmax 0.00668%, amr) (gnomAD).

What do computational predictors say about MAPK10 p.His36Arg (c.107A>G)?

AlphaMissense predicts likely benign (score 0.0922) — an in-silico prediction, not a clinical call.

MAPK10 p.His36Arg

c.107A>G · VCV3870416

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0922 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0922	likely benign
REVEL	0.301	indeterminate
SaProt	LLR -5.46	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 35 kb · p 0.73 · regional, not allelic
Overall
CADD	24.0	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% Admixed American · 4/59,850 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000248% 4/1,612,388 alleles · very rare exomes 4/1,460,286 · genomes 0/152,102 · joint denominator

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: MAPK10
Protein: p.His36Arg
Coding: c.107A>G
MANE Select: NM_138982
Type: single nucleotide variant
Location: chr4:86159427 (GRCh38)
Gene constraint: LOEUF 0.54 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 80.50 · 65 PDB

Full MAPK10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPK10 p.Ala320= Benign ★★ same type
MAPK10 p.Asp351= Benign ★★ same type
MAPK10 p.Val113= Benign/Likely benign ★★ same type
MAPK10 p.Ala353Thr Uncertain significance ★ ⚠ same type
MAPK10 p.Asn89Ser Uncertain significance ★ ⚠ same type
MAPK10 p.Asp141Glu Uncertain significance ★ ⚠ same type
MAPK10 p.Asp267Gly Uncertain significance ★ ⚠ same type
MAPK10 p.Asp315Asn 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/mapk10-p-his36arg (accessed [today's date]).

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