Is MAP3K1 p.Ala671Val (c.2012C>T) pathogenic?

MAP3K1 p.Ala671Val (c.2012C>T) is classified Likely benign in MAP3K1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-29). AlphaMissense: likely benign (0.1131); Ultra-rare (popmax 0.072%, afr); Associated with 46,XY sex reversal 6.

What condition is associated with MAP3K1 p.Ala671Val (c.2012C>T)?

MAP3K1 p.Ala671Val (c.2012C>T) is associated with 46,XY sex reversal 6 (ClinVar).

How common is MAP3K1 p.Ala671Val (c.2012C>T) in the general population?

MAP3K1 p.Ala671Val (c.2012C>T) is ultra-rare (popmax 0.072%, afr) (gnomAD).

What do computational predictors say about MAP3K1 p.Ala671Val (c.2012C>T)?

AlphaMissense predicts likely benign (score 0.1131) — an in-silico prediction, not a clinical call.

MAP3K1 p.Ala671Val

c.2012C>T · rs201310278 · VCV2852904

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1131 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.072%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

46,XY sex reversal 6

Computational evidence

Protein change
AlphaMissense	0.1131	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -7.31	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 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 11 kb · p 0.13 · regional, not allelic
Overall
CADD	23.5	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 0.072% African / African-American · 54/74,970 alleles

Filtering AF 0.0566% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0511%

Overall 0.0132% 213/1,613,752 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.072%	1,388
South Asian	0.0494%	2,024
Remaining individualsnot grpmax-eligible	0.0112%	8,927
European (non-Finnish)	0.00839%	11,917
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,794
East Asian	0.00669%	14,956
Admixed American	0.005%	20,003

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.Ala671Val
Coding: c.2012C>T
MANE Select: NM_005921
dbSNP: rs201310278
Type: single nucleotide variant
Location: chr5:56879026 (GRCh38)
Gene constraint: LOEUF 0.355 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 59.80 · 1 PDB
Residue 671: an α-helix

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.Ala671= 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-ala671val (accessed [today's date]).

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