Is MAP3K7 p.Val594Asp (c.1781T>A) pathogenic?

MAP3K7 p.Val594Asp (c.1781T>A) is classified Uncertain significance in MAP3K7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-22). AlphaMissense: ambiguous (0.35); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MAP3K7 p.Val594Asp (c.1781T>A)?

MAP3K7 p.Val594Asp (c.1781T>A) is associated with Inborn genetic diseases (ClinVar).

How common is MAP3K7 p.Val594Asp (c.1781T>A) in the general population?

MAP3K7 p.Val594Asp (c.1781T>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about MAP3K7 p.Val594Asp (c.1781T>A)?

AlphaMissense predicts ambiguous (score 0.35) — an in-silico prediction, not a clinical call.

MAP3K7 p.Val594Asp

c.1781T>A · rs2534238436 · VCV3123020

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.35 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.35	ambiguous
REVEL	0.321	indeterminate
SaProt	LLR -5.11	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 128 bp · p 0.53 · regional, not allelic
Overall
CADD	24.3	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

Grpmax group 0.00017% European (non-Finnish) · 2/1,178,924 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,612,070 alleles · very rare exomes 2/1,460,212 · genomes 0/151,858 · joint denominator

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.Val594Asp
Coding: c.1781T>A
MANE Select: NM_145331
dbSNP: rs2534238436
Type: single nucleotide variant
Location: chr6:90516541 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.27 · 25 PDB

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.Val594Ile Uncertain significance ★ ⚠ 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
MAP3K7 p.Gly411Asp 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-val594asp (accessed [today's date]).

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