Is MAP3K7 p.Cys96Ser (c.287G>C) pathogenic?

MAP3K7 p.Cys96Ser (c.287G>C) is classified Uncertain significance in MAP3K7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-15). AlphaMissense: likely pathogenic (0.8283); Absent from gnomAD v4.1.

How common is MAP3K7 p.Cys96Ser (c.287G>C) in the general population?

MAP3K7 p.Cys96Ser (c.287G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAP3K7 p.Cys96Ser (c.287G>C)?

AlphaMissense predicts likely pathogenic (score 0.8283) — an in-silico prediction, not a clinical call.

MAP3K7 p.Cys96Ser

c.287G>C · rs2481865550 · VCV2967532

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8283 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8283	likely pathogenic
REVEL	0.66	pathogenic-leaning
SaProt	LLR -8.18	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
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 0.36	constrained · MANE · 35 kb · p 4.4e-26 · regional, not allelic
Overall
CADD	28.2	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

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: MAP3K7
Protein: p.Cys96Ser
Coding: c.287G>C
MANE Select: NM_145331
dbSNP: rs2481865550
Type: single nucleotide variant
Location: chr6:90568568 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.27 · 25 PDB
Residue 96: the protein kinase domain; the 'interaction with mapk8ip1' region; a β-strand

Full MAP3K7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP3K7 p.Arg274Cys Pathogenic/Likely pathogenic ★★ same type
MAP3K7 p.Gly110Ser Pathogenic/Likely pathogenic ★★ same type
MAP3K7 p.Pro512Leu Pathogenic ★★ same type
MAP3K7 p.Ala313Thr Uncertain significance ★★ ⚠ same type
MAP3K7 p.Ala400Thr Uncertain significance ★★ ⚠ same type
MAP3K7 p.Ala6Thr Uncertain significance ★★ ⚠ same type
MAP3K7 p.Arg289Gln Uncertain significance ★★ ⚠ same type
MAP3K7 p.Arg347His 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/map3k7-p-cys96ser (accessed [today's date]).

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