Is MAP2K7 p.Arg85Cys (c.253C>T) pathogenic?

MAP2K7 p.Arg85Cys (c.253C>T) is classified Uncertain significance in MAP2K7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-17). AlphaMissense: ambiguous (0.3566); Very rare (popmax 0.00617%, sas).

How common is MAP2K7 p.Arg85Cys (c.253C>T) in the general population?

MAP2K7 p.Arg85Cys (c.253C>T) is very rare (popmax 0.00617%, sas) (gnomAD).

What do computational predictors say about MAP2K7 p.Arg85Cys (c.253C>T)?

AlphaMissense predicts ambiguous (score 0.3566) — an in-silico prediction, not a clinical call.

MAP2K7 p.Arg85Cys

c.253C>T · rs766635456 · VCV2537381

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3566 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00617%, sas)

Computational evidence

Protein change
AlphaMissense	0.3566	ambiguous
REVEL	0.341	indeterminate
SaProt	LLR -10.01	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 5,951 bp · p 0.32 · regional, not allelic
Overall
CADD	28.1	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 0.00617% South Asian · 5/81,004 alleles

Filtering AF 0.0024% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00151%

Overall 0.00117% 16/1,373,058 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00617%	16,201
Remaining individualsnot grpmax-eligible	0.0017%	58,908
African / African-American	0.00138%	72,422
European (non-Finnish)	0.000794%	125,964

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.Arg85Cys
Coding: c.253C>T
MANE Select: NM_145185
dbSNP: rs766635456
Type: single nucleotide variant
Location: chr19:7909883 (GRCh38)
Gene constraint: LOEUF 0.454 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.94 · 37 PDB

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.Cys131= 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

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-arg85cys (accessed [today's date]).

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