Is MAPK12 p.Arg82His (c.245G>A) pathogenic?

MAPK12 p.Arg82His (c.245G>A) is classified Uncertain significance in MAPK12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely benign (0.0852); Very rare (popmax 0.00137%, afr).

How common is MAPK12 p.Arg82His (c.245G>A) in the general population?

MAPK12 p.Arg82His (c.245G>A) is very rare (popmax 0.00137%, afr) (gnomAD).

What do computational predictors say about MAPK12 p.Arg82His (c.245G>A)?

AlphaMissense predicts likely benign (score 0.0852) — an in-silico prediction, not a clinical call.

MAPK12 p.Arg82His

c.245G>A · rs767106347 · VCV3123223

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0852 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00137%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0852	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -8.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.95	GERP -2.5, phastCons 0.44
Regional constraint	o/e 1.10	unconstrained · MANE · 8,105 bp · p 0.021 · regional, not allelic
Overall
CADD	26.8	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 0.00137% African / African-American · 1/73,184 alleles

Filtering AF 0.000185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000503% 8/1,590,184 alleles · very rare exomes 8/1,437,888 · genomes 0/152,296 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00137%	73,184
South Asian	0.00113%	88,194
European (non-Finnish)	0.000513%	194,857

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: MAPK12
Protein: p.Arg82His
Coding: c.245G>A
MANE Select: NM_002969
dbSNP: rs767106347
Type: single nucleotide variant
Location: chr22:50261177 (GRCh38)
Gene constraint: LOEUF 1.387 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.33 · 4 PDB
Residue 82: the protein kinase domain

Full MAPK12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPK12 p.Arg82Cys Uncertain significance ★ ⚠ same residue
MAPK12 p.Ala146Thr Uncertain significance ★ ⚠ same type
MAPK12 p.Ala175Val Uncertain significance ★ ⚠ same type
MAPK12 p.Ala296Thr Uncertain significance ★ ⚠ same type
MAPK12 p.Arg129Trp Uncertain significance ★ same type
MAPK12 p.Arg189Gln Uncertain significance ★ ⚠ same type
MAPK12 p.Arg189Trp Uncertain significance ★ ⚠ same type
MAPK12 p.Arg192Gln 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/mapk12-p-arg82his (accessed [today's date]).

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