Is MAP3K1 p.Ala229Val (c.686C>T) pathogenic?

MAP3K1 p.Ala229Val (c.686C>T) is classified Uncertain significance in MAP3K1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-17). AlphaMissense: likely benign (0.0857); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MAP3K1 p.Ala229Val (c.686C>T)?

MAP3K1 p.Ala229Val (c.686C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MAP3K1 p.Ala229Val (c.686C>T) in the general population?

MAP3K1 p.Ala229Val (c.686C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAP3K1 p.Ala229Val (c.686C>T)?

AlphaMissense predicts likely benign (score 0.0857) — an in-silico prediction, not a clinical call.

MAP3K1 p.Ala229Val

c.686C>T · rs1747447963 · VCV3122814

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0857 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0857	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -6.87	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 4.1	GERP 1.8, phastCons 0.55
Regional constraint	o/e 0.84	unconstrained · MANE · 8,192 bp · p 0.028 · regional, not allelic
Overall
CADD	17.64	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAP3K1
Protein: p.Ala229Val
Coding: c.686C>T
MANE Select: NM_005921
dbSNP: rs1747447963
Type: single nucleotide variant
Location: chr5:56859767 (GRCh38)
Gene constraint: LOEUF 0.355 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 59.80 · 1 PDB
Residue 229: 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

Similar variants

MAP3K1 p.Ala594Ser Uncertain significance ★★ ⚠ same condition
MAP3K1 p.Arg204Lys Uncertain significance ★★ ⚠ same condition
MAP3K1 p.Val1346Ile Uncertain significance ★★ ⚠ same condition
MAP3K1 p.Pro962= Benign/Likely benign ★★ same condition
MAP3K1 p.Leu189Gln Likely pathogenic ★ ⚠ same condition
MAP3K1 p.Ala1017Val Uncertain significance ★ ⚠ same condition
MAP3K1 p.Ala1327Pro Uncertain significance ★ ⚠ same condition
MAP3K1 p.Ala1402Gly Uncertain significance ★ ⚠ 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-ala229val (accessed [today's date]).

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