Is MAP3K7 p.Arg83His (c.248G>A) pathogenic?

MAP3K7 p.Arg83His (c.248G>A) is classified Conflicting classifications of pathogenicity in MAP3K7 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-01). AlphaMissense: likely pathogenic (0.9835); No allele count reported in gnomAD v4.1 (AN 1,608,210); Associated with cardiospondylocarpofacial syndrome.

What condition is associated with MAP3K7 p.Arg83His (c.248G>A)?

MAP3K7 p.Arg83His (c.248G>A) is associated with cardiospondylocarpofacial syndrome (ClinVar).

How common is MAP3K7 p.Arg83His (c.248G>A) in the general population?

MAP3K7 p.Arg83His (c.248G>A) is no allele count reported in gnomAD v4.1 (AN 1,608,210) (gnomAD).

What do computational predictors say about MAP3K7 p.Arg83His (c.248G>A)?

AlphaMissense predicts likely pathogenic (score 0.9835) — an in-silico prediction, not a clinical call.

MAP3K7 p.Arg83His

c.248G>A · rs929527043 · VCV689611

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9835 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,608,210)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cardiospondylocarpofacial syndrome

Computational evidence

Protein change
AlphaMissense	0.9835	likely pathogenic
REVEL	0.711	pathogenic-leaning
SaProt	LLR -12.74	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.36	constrained · MANE · 35 kb · p 4.4e-26 · regional, not allelic
Overall
CADD	33.0	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

No allele count reported in gnomAD v4.1 (AN 1,608,210). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MAP3K7
Protein: p.Arg83His
Coding: c.248G>A
MANE Select: NM_145331
dbSNP: rs929527043
Type: single nucleotide variant
Location: chr6:90568607 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.27 · 25 PDB
Residue 83: the protein kinase domain; the 'interaction with mapk8ip1' region; an α-helix

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

Disease context

cardiospondylocarpofacial syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAP3K7 p.Arg83Cys Uncertain significance ★ ⚠ same residue
MAP3K7 p.Arg83= Likely benign ★ same residue
MAP3K7 p.Gly110Cys Likely pathogenic ★ same condition
MAP3K7 p.Ser192Asn Likely pathogenic ★ same condition
MAP3K7 p.Ser272Tyr Likely pathogenic ★ ⚠ same condition
MAP3K7 p.Trp241Arg Pathogenic ★ same condition
MAP3K7 p.Tyr206Asp Pathogenic ★ same condition
MAP3K7 c.737-7A>G Conflicting classifications of pathogenicity ★ 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/map3k7-p-arg83his (accessed [today's date]).

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