Is MAP3K1 p.Arg339Gln (c.1016G>A) pathogenic?

MAP3K1 p.Arg339Gln (c.1016G>A) is classified Pathogenic in MAP3K1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-03). AlphaMissense: likely pathogenic (0.6473); Absent from gnomAD v4.1; Associated with 46,XY sex reversal 6.

What condition is associated with MAP3K1 p.Arg339Gln (c.1016G>A)?

MAP3K1 p.Arg339Gln (c.1016G>A) is associated with 46,XY sex reversal 6 (ClinVar).

How common is MAP3K1 p.Arg339Gln (c.1016G>A) in the general population?

MAP3K1 p.Arg339Gln (c.1016G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAP3K1 p.Arg339Gln (c.1016G>A)?

AlphaMissense predicts likely pathogenic (score 0.6473) — an in-silico prediction, not a clinical call.

MAP3K1 p.Arg339Gln

c.1016G>A · rs1554034036 · VCV471688

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6473 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

46,XY sex reversal 6

Computational evidence

Protein change
AlphaMissense	0.6473	likely pathogenic ✓ concordant with ClinVar
REVEL	0.786	moderately pathogenic-leaning
SaProt	LLR -8.05	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 507 bp · p 3.3e-06 · regional, not allelic
Overall
CADD	32.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAP3K1
Protein: p.Arg339Gln
Coding: c.1016G>A
MANE Select: NM_005921
dbSNP: rs1554034036
Type: single nucleotide variant
Location: chr5:56864915 (GRCh38)
Gene constraint: LOEUF 0.355 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 59.80 · 1 PDB

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.Arg339Trp Likely benign ★ same residue
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

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-arg339gln (accessed [today's date]).

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