Is MAP3K8 p.Arg302= (c.906G>A) pathogenic?

MAP3K8 p.Arg302= (c.906G>A) is classified Likely benign in MAP3K8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-01-30). Very rare (popmax 0.000428%, nfe); Associated with MAP3K8-related disorder.

What condition is associated with MAP3K8 p.Arg302= (c.906G>A)?

MAP3K8 p.Arg302= (c.906G>A) is associated with MAP3K8-related disorder (ClinVar).

How common is MAP3K8 p.Arg302= (c.906G>A) in the general population?

MAP3K8 p.Arg302= (c.906G>A) is very rare (popmax 0.000428%, nfe) (gnomAD).

MAP3K8 p.Arg302=

c.906G>A · rs1437312394 · VCV3053061

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000428%, nfe)

Conditions

MAP3K8-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.2	GERP -1.5, phastCons 1
Overall
CADD	6.607	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000428% European (non-Finnish) · 5/1,167,710 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000314% 5/1,589,962 alleles · very rare exomes 5/1,437,688 · genomes 0/152,274 · joint denominator

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: MAP3K8
Protein: p.Arg302=
Coding: c.906G>A
MANE Select: NM_005204
dbSNP: rs1437312394
Type: single nucleotide variant
Location: chr10:30458116 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI 0.73 (gnomAD)
Structure: AlphaFold pLDDT 74.13 · 3 PDB
Residue 302: the protein kinase domain

Full MAP3K8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MAP3K8-related disorder

Similar variants

MAP3K8 p.Pro116Thr Uncertain significance ★ ⚠ same condition
MAP3K8 p.Met262Leu Uncertain significance ⚠ same condition
MAP3K8 p.Ala35Ser Uncertain significance ★★ ⚠ same type
MAP3K8 p.Ala450Thr Uncertain significance ★★ same type
MAP3K8 p.Arg392Gly Uncertain significance ★★ ⚠ same type
MAP3K8 p.Arg408Ser Uncertain significance ★★ ⚠ same type
MAP3K8 p.Asn54Asp Uncertain significance ★★ ⚠ same type
MAP3K8 p.Gly67Asp Uncertain significance ★★ ⚠ same type

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/map3k8-p-arg302 (accessed [today's date]).

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