Is MAP3K1 p.Thr985del (c.2953_2955del) pathogenic?

MAP3K1 p.Thr985del (c.29532955del) is classified Benign in MAP3K1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-15). Low-frequency (popmax 2.6%, afr); Associated with 46,XY sex reversal 6.

What condition is associated with MAP3K1 p.Thr985del (c.2953_2955del)?

MAP3K1 p.Thr985del (c.2953_2955del) is associated with 46,XY sex reversal 6 (ClinVar).

How common is MAP3K1 p.Thr985del (c.2953_2955del) in the general population?

MAP3K1 p.Thr985del (c.2953_2955del) is low-frequency (popmax 2.6%, afr) (gnomAD).

MAP3K1 p.Thr985del

c.2953_2955del · rs140733770 · VCV766843

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.6%, afr)

Conditions

46,XY sex reversal 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.47	GERP -4.9
Overall
CADD	2.759	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.6% African / African-American · 1,951/75,026 alleles

Filtering AF 2.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.47%

Overall 0.137% 2,218/1,614,124 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.6%	38
Remaining individualsnot grpmax-eligible	0.211%	474
Admixed American	0.162%	618
Middle Eastern	0.132%	758
South Asian	0.00439%	22,770
European (non-Finnish)	0.0022%	45,385

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.Thr985del
Coding: c.2953_2955del
MANE Select: NM_005921
dbSNP: rs140733770
Type: Deletion
Location: chr5:56882153 (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.Ser928del Uncertain significance ★ same condition
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-thr985del (accessed [today's date]).

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