Is MAP2K7 p.Cys131= (c.393C>T) pathogenic?

MAP2K7 p.Cys131= (c.393C>T) is classified Benign in MAP2K7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Common (popmax 9.67%, afr) — too common for a highly-penetrant pathogenic allele.

MAP2K7 p.Cys131=

Q: How common is MAP2K7 p.Cys131= (c.393C>T) in the general population?

MAP2K7 p.Cys131= (c.393C>T) is common (popmax 9.67%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.393C>T · rs28395773 · VCV777407

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 9.67%, afr) — too common for a highly-penetrant pathogenic allele

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 -12	GERP -3.1
Overall
CADD	2.205	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.67% African / African-American · 7,258/75,030 alleles

Filtering AF 9.49% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.41%

Overall 0.539% 8,695/1,613,268 alleles · common exomes 4,402/1,460,952 · genomes 4,293/152,316 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.67%	10
Admixed American	0.888%	113
Remaining individualsnot grpmax-eligible	0.701%	143
Ashkenazi Jewishnot grpmax-eligible	0.365%	274
Middle Eastern	0.363%	276
South Asian	0.0318%	3,141
European (non-Finnish)	0.0259%	3,856
Finnishnot grpmax-eligible	0.00158%	63,260

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: MAP2K7
Protein: p.Cys131=
Coding: c.393C>T
MANE Select: NM_145185
dbSNP: rs28395773
Type: single nucleotide variant
Location: chr19:7910319 (GRCh38)
Gene constraint: LOEUF 0.454 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.94 · 37 PDB
Residue 131: a binding site; the protein kinase domain; a β-strand

Full MAP2K7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP2K7 c.855+10G>C Benign ★★ same type
MAP2K7 c.856-19T>C Benign ★★ same type
MAP2K7 c.856-8C>G Benign ★★ same type
MAP2K7 p.Pro215= Benign ★★ same type
MAP2K7 p.Ser277= Benign ★★ same type
MAP2K7 p.Ala391Val Uncertain significance ★ same type
MAP2K7 p.Ala399Val Uncertain significance ★ ⚠ same type
MAP2K7 p.Arg12Leu Uncertain significance ★ 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/map2k7-p-cys131 (accessed [today's date]).

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