Is MAP3K1 p.Glu601Lys (c.1801G>A) pathogenic?

MAP3K1 p.Glu601Lys (c.1801G>A) is classified Likely benign in MAP3K1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). AlphaMissense: likely pathogenic (0.622); Ultra-rare (popmax 0.0245%, eas); Associated with 46,XY sex reversal 6.

What condition is associated with MAP3K1 p.Glu601Lys (c.1801G>A)?

MAP3K1 p.Glu601Lys (c.1801G>A) is associated with 46,XY sex reversal 6 (ClinVar).

How common is MAP3K1 p.Glu601Lys (c.1801G>A) in the general population?

MAP3K1 p.Glu601Lys (c.1801G>A) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

What do computational predictors say about MAP3K1 p.Glu601Lys (c.1801G>A)?

AlphaMissense predicts likely pathogenic (score 0.622) — an in-silico prediction, not a clinical call.

MAP3K1 p.Glu601Lys

c.1801G>A · rs761556838 · VCV2152000

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.622 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

46,XY sex reversal 6

Computational evidence

Protein change
AlphaMissense	0.622	likely pathogenic
REVEL	0.271	benign-leaning
SaProt	LLR -6.24	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 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 11 kb · p 0.13 · regional, not allelic
Overall
CADD	27.3	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 0.0245% East Asian · 11/44,892 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.000743% 12/1,614,078 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,081
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Glu601Lys
Coding: c.1801G>A
MANE Select: NM_005921
dbSNP: rs761556838
Type: single nucleotide variant
Location: chr5:56875146 (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.Glu601= 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-glu601lys (accessed [today's date]).

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