Is MAP3K7 p.Leu352= (c.1056G>A) pathogenic?

MAP3K7 p.Leu352= (c.1056G>A) is classified Likely benign in MAP3K7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-23). Very rare (popmax 8.49e-05%, nfe); Associated with MAP3K7-related disorder.

What condition is associated with MAP3K7 p.Leu352= (c.1056G>A)?

MAP3K7 p.Leu352= (c.1056G>A) is associated with MAP3K7-related disorder (ClinVar).

How common is MAP3K7 p.Leu352= (c.1056G>A) in the general population?

MAP3K7 p.Leu352= (c.1056G>A) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

MAP3K7 p.Leu352=

c.1056G>A · rs758604367 · VCV3038657

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Conditions

MAP3K7-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.1	GERP -3.8, phastCons 0.46
Overall
CADD	4.942	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,178,392 alleles

Overall 0.000124% 2/1,610,168 alleles · very rare exomes 2/1,457,974 · genomes 0/152,194 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,332
European (non-Finnish)grpmax	8.49e-05%	1,178,392

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu352=
Coding: c.1056G>A
MANE Select: NM_145331
dbSNP: rs758604367
Type: single nucleotide variant
Location: chr6:90548071 (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

MAP3K7-related disorder

Similar variants

MAP3K7 p.Gly168Arg Pathogenic ★ same condition
MAP3K7 p.Ser310Gly Uncertain significance ★ ⚠ same condition
MAP3K7 p.Asn329Ile Uncertain significance ⚠ same condition
MAP3K7 p.Val50del Pathogenic/Likely pathogenic ★★ same condition
MAP3K7 p.Arg155_Asp156delinsAsn Likely pathogenic ★ same condition
MAP3K7 p.His185_Thr187del Likely pathogenic ★ same condition
MAP3K7 p.Arg274Cys Pathogenic/Likely pathogenic ★★ same type
MAP3K7 p.Gly110Ser Pathogenic/Likely pathogenic ★★ same type

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-leu352 (accessed [today's date]).

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