Is MAP2K7 p.Asn189Ser (c.566A>G) pathogenic?

MAP2K7 p.Asn189Ser (c.566A>G) is classified Uncertain significance in MAP2K7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: likely benign (0.0835); Ultra-rare (popmax 0.0155%, nfe).

How common is MAP2K7 p.Asn189Ser (c.566A>G) in the general population?

MAP2K7 p.Asn189Ser (c.566A>G) is ultra-rare (popmax 0.0155%, nfe) (gnomAD).

What do computational predictors say about MAP2K7 p.Asn189Ser (c.566A>G)?

AlphaMissense predicts likely benign (score 0.0835) — an in-silico prediction, not a clinical call.

MAP2K7 p.Asn189Ser

c.566A>G · rs199553372 · VCV2347560

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0835 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0155%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0835	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -6.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.9	GERP 0.53, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 1,458 bp · p 2.3e-17 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0155% European (non-Finnish) · 183/1,179,958 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.0115% 185/1,613,358 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0155%	6,448
Remaining individualsnot grpmax-eligible	0.0032%	31,235

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.Asn189Ser
Coding: c.566A>G
MANE Select: NM_145185
dbSNP: rs199553372
Type: single nucleotide variant
Location: chr19:7910571 (GRCh38)
Gene constraint: LOEUF 0.454 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.94 · 37 PDB
Residue 189: 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.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-asn189ser (accessed [today's date]).

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