Is MAP3K2 p.Thr293= (c.879C>A) pathogenic?

MAP3K2 p.Thr293= (c.879C>A) is classified Benign in MAP3K2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-03-29). Common (popmax 5.04%, afr) — too common for a highly-penetrant pathogenic allele.

MAP3K2 p.Thr293=

Q: How common is MAP3K2 p.Thr293= (c.879C>A) in the general population?

MAP3K2 p.Thr293= (c.879C>A) is common (popmax 5.04%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.879C>A · rs79135681 · VCV712362

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.04%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.9	GERP -1.5, phastCons 1
Overall
CADD	5.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.04% African / African-American · 3,779/74,992 alleles

Filtering AF 4.91% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.85%

Overall 0.274% 4,414/1,613,846 alleles · common exomes 2,254/1,461,636 · genomes 2,160/152,210 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.04%	20
Remaining individualsnot grpmax-eligible	0.394%	254
Middle Eastern	0.379%	264
Admixed American	0.357%	280
South Asian	0.0132%	7,589
European (non-Finnish)	0.0119%	8,427

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: MAP3K2
Protein: p.Thr293=
Coding: c.879C>A
MANE Select: NM_001371910
dbSNP: rs79135681
Type: single nucleotide variant
Location: chr2:127322212 (GRCh38)
Gene constraint: LOEUF 0.6 · pLI 0.79 (gnomAD)
Structure: AlphaFold pLDDT 68.27 · 9 PDB
Residue 293: the 'disordered' region

Full MAP3K2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP3K2 p.Tyr422= Benign ★★ same type
MAP3K2 p.Ala178Val Uncertain significance ★ ⚠ same type
MAP3K2 p.Ala487Thr Uncertain significance ★ ⚠ same type
MAP3K2 p.Ala607Thr Uncertain significance ★ ⚠ same type
MAP3K2 p.Arg151Trp Uncertain significance ★ ⚠ same type
MAP3K2 p.Arg286Ile Uncertain significance ★ ⚠ same type
MAP3K2 p.Arg328Lys Uncertain significance ★ ⚠ same type
MAP3K2 p.Arg465His 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/map3k2-p-thr293 (accessed [today's date]).

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