Is MAP3K7 p.Glu66fs (c.197_200del) pathogenic?

MAP3K7 p.Glu66fs (c.197200del) is classified Uncertain significance in MAP3K7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). Associated with cardiospondylocarpofacial syndrome.

What condition is associated with MAP3K7 p.Glu66fs (c.197_200del)?

MAP3K7 p.Glu66fs (c.197_200del) is associated with cardiospondylocarpofacial syndrome (ClinVar).

MAP3K7 p.Glu66fs

c.197_200del · VCV4819633

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

cardiospondylocarpofacial syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 2 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP 0.34, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: MAP3K7
Protein: p.Glu66fs
Coding: c.197_200del
MANE Select: NM_145331
Type: Deletion
Location: chr6:90571728 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.27 · 25 PDB
Residue 66: the protein kinase domain; the 'interaction with mapk8ip1' region

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.Arg44_Gly45del Pathogenic same condition
MAP3K7 p.Val50del Pathogenic/Likely pathogenic ★★ same condition
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 p.Val42del Likely pathogenic ★ 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-glu66fs (accessed [today's date]).

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