Is MAP3K1 p.Gln237Arg (c.710A>G) pathogenic?

MAP3K1 p.Gln237Arg (c.710A>G) is classified Benign/Likely benign in MAP3K1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-11). AlphaMissense: likely benign (0.086); Low-frequency (popmax 2.21%, mid); Associated with 46,XY sex reversal 6.

What condition is associated with MAP3K1 p.Gln237Arg (c.710A>G)?

MAP3K1 p.Gln237Arg (c.710A>G) is associated with 46,XY sex reversal 6 (ClinVar).

How common is MAP3K1 p.Gln237Arg (c.710A>G) in the general population?

MAP3K1 p.Gln237Arg (c.710A>G) is low-frequency (popmax 2.21%, mid) (gnomAD).

What do computational predictors say about MAP3K1 p.Gln237Arg (c.710A>G)?

AlphaMissense predicts likely benign (score 0.086) — an in-silico prediction, not a clinical call.

MAP3K1 p.Gln237Arg

c.710A>G · rs55694258 · VCV252655

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.086 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.21%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

46,XY sex reversal 6

Computational evidence

Protein change
AlphaMissense	0.086	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -4.46	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 0.47	GERP -5.2, phastCons 0.001
Regional constraint	o/e 0.84	unconstrained · MANE · 8,192 bp · p 0.028 · regional, not allelic
Overall
CADD	5.828	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 2.21% Middle Eastern · 134/6,058 alleles

Filtering AF 1.91% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.79%

Overall 0.094% 1,517/1,614,096 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.21%	45
Admixed American	0.355%	282
South Asian	0.193%	517
Remaining individualsnot grpmax-eligible	0.17%	590
Ashkenazi Jewishnot grpmax-eligible	0.152%	658
European (non-Finnish)	0.0679%	1,473
African / African-American	0.0533%	1,877
Finnishnot grpmax-eligible	0.00312%	32,013

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: MAP3K1
Protein: p.Gln237Arg
Coding: c.710A>G
MANE Select: NM_005921
dbSNP: rs55694258
Type: single nucleotide variant
Location: chr5:56859791 (GRCh38)
Gene constraint: LOEUF 0.355 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 59.80 · 1 PDB
Residue 237: the 'disordered' region

Full MAP3K1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

46,XY sex reversal 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAP3K1 p.Arg186Gly Pathogenic/Likely pathogenic ★★ ⚠ same condition
MAP3K1 p.Ala594Ser Uncertain significance ★★ ⚠ same condition
MAP3K1 p.Arg204Lys Uncertain significance ★★ ⚠ same condition
MAP3K1 p.Gln548Glu Uncertain significance ★★ ⚠ same condition
MAP3K1 c.1035+12C>T Likely benign ★★ same condition
MAP3K1 c.1687-46C>G Benign ★★ same condition
MAP3K1 c.2179+16T>G Benign/Likely benign ★★ same condition
MAP3K1 c.3820-11A>G Benign ★★ same condition

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/map3k1-p-gln237arg (accessed [today's date]).

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