Is MAP2K7 p.Lys367Asn (c.1101G>T) pathogenic?

MAP2K7 p.Lys367Asn (c.1101G>T) is classified Uncertain significance in MAP2K7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: ambiguous (0.5579); Very rare (popmax 0.00364%, nfe).

How common is MAP2K7 p.Lys367Asn (c.1101G>T) in the general population?

MAP2K7 p.Lys367Asn (c.1101G>T) is very rare (popmax 0.00364%, nfe) (gnomAD).

What do computational predictors say about MAP2K7 p.Lys367Asn (c.1101G>T)?

AlphaMissense predicts ambiguous (score 0.5579) — an in-silico prediction, not a clinical call.

MAP2K7 p.Lys367Asn

c.1101G>T · VCV4549359

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5579 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00364%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5579	ambiguous
REVEL	0.097	moderately benign-leaning
SaProt	LLR -9.94	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 1.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 906 bp · p 0.27 · regional, not allelic
Overall
CADD	24.8	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 0.00364% European (non-Finnish) · 43/1,179,992 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00301% 44/1,461,718 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00364%	27,442
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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.Lys367Asn
Coding: c.1101G>T
MANE Select: NM_145185
Type: single nucleotide variant
Location: chr19:7912170 (GRCh38)
Gene constraint: LOEUF 0.454 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.94 · 37 PDB
Residue 367: the protein kinase domain; an α-helix

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-lys367asn (accessed [today's date]).

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