Is MAP3K2 p.Gly313Arg (c.937G>A) pathogenic?

MAP3K2 p.Gly313Arg (c.937G>A) is classified Uncertain significance in MAP3K2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-14). AlphaMissense: likely pathogenic (0.8872); Very rare (popmax 0.005%, amr).

How common is MAP3K2 p.Gly313Arg (c.937G>A) in the general population?

MAP3K2 p.Gly313Arg (c.937G>A) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about MAP3K2 p.Gly313Arg (c.937G>A)?

AlphaMissense predicts likely pathogenic (score 0.8872) — an in-silico prediction, not a clinical call.

MAP3K2 p.Gly313Arg

c.937G>A · VCV3870208

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8872 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8872	likely pathogenic
REVEL	0.15	moderately benign-leaning
SaProt	LLR -6.89	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 25 kb · p 0.016 · regional, not allelic
Overall
CADD	24.0	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 0.005% Admixed American · 3/59,992 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00112% 18/1,613,676 alleles · very rare exomes 15/1,461,516 · genomes 3/152,160 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,997
Remaining individualsnot grpmax-eligible	0.0032%	31,229
African / African-American	0.00133%	74,910
European (non-Finnish)	0.00102%	98,313

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.Gly313Arg
Coding: c.937G>A
MANE Select: NM_001371910
Type: single nucleotide variant
Location: chr2:127322154 (GRCh38)
Gene constraint: LOEUF 0.6 · pLI 0.79 (gnomAD)
Structure: AlphaFold pLDDT 68.27 · 9 PDB
Residue 313: the 'disordered' region

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

Similar variants

MAP3K2 p.Thr293= Benign ★★ same type
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

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-gly313arg (accessed [today's date]).

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