Is MAP3K7 p.Ala73Val (c.218C>T) pathogenic?

MAP3K7 p.Ala73Val (c.218C>T) is classified Uncertain significance in MAP3K7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: likely pathogenic (0.9928); Very rare (popmax 0.00178%, amr); Associated with Inborn genetic diseases.

What condition is associated with MAP3K7 p.Ala73Val (c.218C>T)?

MAP3K7 p.Ala73Val (c.218C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MAP3K7 p.Ala73Val (c.218C>T) in the general population?

MAP3K7 p.Ala73Val (c.218C>T) is very rare (popmax 0.00178%, amr) (gnomAD).

What do computational predictors say about MAP3K7 p.Ala73Val (c.218C>T)?

AlphaMissense predicts likely pathogenic (score 0.9928) — an in-silico prediction, not a clinical call.

MAP3K7 p.Ala73Val

c.218C>T · rs773394242 · VCV3123021

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9928 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9928	likely pathogenic
REVEL	0.615	indeterminate
SaProt	LLR -10.96	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.36	constrained · MANE · 35 kb · p 4.4e-26 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00178% Admixed American · 1/56,128 alleles

Overall 0.000126% 2/1,583,704 alleles · very rare exomes 2/1,431,746 · genomes 0/151,958 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00178%	56,128
European (non-Finnish)	8.59e-05%	1,164,184

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: MAP3K7
Protein: p.Ala73Val
Coding: c.218C>T
MANE Select: NM_145331
dbSNP: rs773394242
Type: single nucleotide variant
Location: chr6:90571710 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.27 · 25 PDB
Residue 73: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAP3K7 p.Ala73Thr Uncertain significance ★ ⚠ same residue
MAP3K7 p.Ala73= Likely benign ★ same residue
MAP3K7 p.Ala313Thr Uncertain significance ★★ ⚠ same condition
MAP3K7 p.Ala400Thr Uncertain significance ★★ ⚠ same condition
MAP3K7 p.Ala6Thr Uncertain significance ★★ ⚠ same condition
MAP3K7 p.Arg289Gln Uncertain significance ★★ ⚠ same condition
MAP3K7 p.Arg347His Uncertain significance ★★ ⚠ same condition
MAP3K7 p.Asn342Asp 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-ala73val (accessed [today's date]).

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