Is MAP3K7 p.Val100Glu (c.299T>A) pathogenic?

MAP3K7 p.Val100Glu (c.299T>A) is classified Pathogenic in MAP3K7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-02-04). AlphaMissense: likely pathogenic (0.9938); Absent from gnomAD v4.1; Associated with frontometaphyseal dysplasia 2.

What condition is associated with MAP3K7 p.Val100Glu (c.299T>A)?

MAP3K7 p.Val100Glu (c.299T>A) is associated with frontometaphyseal dysplasia 2 (ClinVar).

How common is MAP3K7 p.Val100Glu (c.299T>A) in the general population?

MAP3K7 p.Val100Glu (c.299T>A) is absent from gnomAD v4.1 (gnomAD).

How is Frontometaphyseal dysplasia inherited?

Typically Autosomal dominant, X-linked dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MAP3K7 p.Val100Glu (c.299T>A)?

AlphaMissense predicts likely pathogenic (score 0.9938) — an in-silico prediction, not a clinical call.

MAP3K7 p.Val100Glu

c.299T>A · rs886039232 · VCV264700

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9938 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

frontometaphyseal dysplasia 2

Computational evidence

Protein change
AlphaMissense	0.9938	likely pathogenic ✓ concordant with ClinVar
REVEL	0.749	pathogenic-leaning
SaProt	LLR -10.74	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	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

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.Val100Glu
Coding: c.299T>A
MANE Select: NM_145331
dbSNP: rs886039232
Type: single nucleotide variant
Location: chr6:90561666 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.27 · 25 PDB
Residue 100: the protein kinase domain; the 'interaction with mapk8ip1' region; a UniProt-annotated variant site (in fmd2); a β-strand

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

Disease context

frontometaphyseal dysplasia 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Frontometaphyseal dysplasia (Orphanet):

Inheritance: Autosomal dominant, X-linked dominant
Onset: Neonatal

Similar variants

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MAP3K7 p.Gly451Ser Uncertain significance ★★ ⚠ same condition
MAP3K7 p.Gly110Asp Pathogenic ★ same condition
MAP3K7 p.Gly168Arg Pathogenic ★ same condition
MAP3K7 p.Ser272Tyr Likely pathogenic ★ ⚠ same condition
MAP3K7 c.1356+9A>G Uncertain significance ★ same condition
MAP3K7 p.Arg265Cys Uncertain significance ★ ⚠ same condition
MAP3K7 p.Met388Val 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/map3k7-p-val100glu (accessed [today's date]).

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