Is MAP3K1 p.Pro962= (c.2886C>G) pathogenic?

MAP3K1 p.Pro962= (c.2886C>G) is classified Benign/Likely benign in MAP3K1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-05). Rare (popmax 0.449%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MAP3K1 p.Pro962= (c.2886C>G)?

MAP3K1 p.Pro962= (c.2886C>G) is associated with Inborn genetic diseases, 46,XY sex reversal 6 (ClinVar).

How common is MAP3K1 p.Pro962= (c.2886C>G) in the general population?

MAP3K1 p.Pro962= (c.2886C>G) is rare (popmax 0.449%, nfe) (gnomAD).

MAP3K1 p.Pro962=

c.2886C>G · rs201198197 · VCV766965

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.449%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.83, phastCons 1
Overall
CADD	9.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.449% European (non-Finnish) · 5,293/1,180,024 alleles

Filtering AF 0.438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.434%

Overall 0.363% 5,864/1,614,098 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.449%	223
Remaining individualsnot grpmax-eligible	0.37%	271
Admixed American	0.248%	403
Finnishnot grpmax-eligible	0.169%	593
African / African-American	0.0773%	1,293
Ashkenazi Jewishnot grpmax-eligible	0.0507%	1,973
Middle Eastern	0.0495%	2,021
South Asian	0.00768%	13,013

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.Pro962=
Coding: c.2886C>G
MANE Select: NM_005921
dbSNP: rs201198197
Type: single nucleotide variant
Location: chr5:56882086 (GRCh38)
Gene constraint: LOEUF 0.355 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 59.80 · 1 PDB
Residue 962: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: 46,XY sex reversal 6

Similar variants

MAP3K1 p.Pro962Ala Uncertain significance ★ ⚠ same residue
MAP3K1 p.Pro962Thr Uncertain significance ★ ⚠ 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 p.Val1346Ile Uncertain significance ★★ ⚠ same condition
MAP3K1 c.1035+12C>T 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-pro962 (accessed [today's date]).

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