Is MAP2K3 p.Arg293His (c.878G>A) pathogenic?

MAP2K3 p.Arg293His (c.878G>A) is classified Benign in MAP2K3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-04). AlphaMissense: likely benign (0.0812); Ultra-rare (popmax 0.0235%, sas).

How common is MAP2K3 p.Arg293His (c.878G>A) in the general population?

MAP2K3 p.Arg293His (c.878G>A) is ultra-rare (popmax 0.0235%, sas) (gnomAD).

What do computational predictors say about MAP2K3 p.Arg293His (c.878G>A)?

AlphaMissense predicts likely benign (score 0.0812) — an in-silico prediction, not a clinical call.

MAP2K3 p.Arg293His

c.878G>A · rs35206134 · VCV768859

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0812 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0235%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0812	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -9.64	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 1.4	GERP -5.1, phastCons 0.78
Regional constraint	o/e 0.77	unconstrained · MANE · 2,006 bp · p 0.04 · regional, not allelic
Overall
CADD	15.61	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0235% South Asian · 21/89,544 alleles

Filtering AF 0.0156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0131%

Overall 0.00487% 78/1,601,516 alleles · ultra-rare exomes 71/1,449,206 · genomes 7/152,310 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0235%	4,264
Admixed American	0.0158%	6,347
Remaining individualsnot grpmax-eligible	0.00646%	15,481
European (non-Finnish)	0.00357%	27,996
African / African-American	0.00271%	36,944

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: MAP2K3
Protein: p.Arg293His
Coding: c.878G>A
MANE Select: NM_145109
dbSNP: rs35206134
Type: single nucleotide variant
Location: chr17:21312245 (GRCh38)
Gene constraint: LOEUF 0.993 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.13
Residue 293: the protein kinase domain; a UniProt-annotated variant site (in)

Full MAP2K3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP2K3 p.Leu215Trp Uncertain significance ★★ ⚠ same type
MAP2K3 c.568+10C>T Benign ★★ same type
MAP2K3 p.Ala220= Benign ★★ same type
MAP2K3 p.Ala225= Likely benign ★★ same type
MAP2K3 p.Leu25= Benign ★★ same type
MAP2K3 p.Leu319= Likely benign ★★ same type
MAP2K3 p.Pro40Thr Benign ★★ same type
MAP2K3 p.Ser286= Likely benign ★★ 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/map2k3-p-arg293his (accessed [today's date]).

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