Is MAP3K1 p.Asn899Ser (c.2696A>G) pathogenic?

MAP3K1 p.Asn899Ser (c.2696A>G) is classified Conflicting classifications of pathogenicity in MAP3K1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-10-05). AlphaMissense: likely benign (0.0789); Very rare (popmax 0.00666%, afr); Associated with Inborn genetic diseases.

What condition is associated with MAP3K1 p.Asn899Ser (c.2696A>G)?

MAP3K1 p.Asn899Ser (c.2696A>G) is associated with Inborn genetic diseases, 46,XY sex reversal 6 (ClinVar).

How common is MAP3K1 p.Asn899Ser (c.2696A>G) in the general population?

MAP3K1 p.Asn899Ser (c.2696A>G) is very rare (popmax 0.00666%, afr) (gnomAD).

What do computational predictors say about MAP3K1 p.Asn899Ser (c.2696A>G)?

AlphaMissense predicts likely benign (score 0.0789) — an in-silico prediction, not a clinical call.

MAP3K1 p.Asn899Ser

c.2696A>G · rs142968004 · VCV833601

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0789 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0789	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -5.54	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 0.058	GERP -1.3
Regional constraint	o/e 0.95	unconstrained · MANE · 11 kb · p 0.13 · regional, not allelic
Overall
CADD	0.103	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 0.00666% African / African-American · 5/75,032 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000558% 9/1,614,136 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00666%	15,006
Remaining individualsnot grpmax-eligible	0.0048%	20,835
European (non-Finnish)	8.47e-05%	1,180,022

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.Asn899Ser
Coding: c.2696A>G
MANE Select: NM_005921
dbSNP: rs142968004
Type: single nucleotide variant
Location: chr5:56881896 (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

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.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
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-asn899ser (accessed [today's date]).

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