Is MAP2K7 p.Ile34Met (c.102C>G) pathogenic?

MAP2K7 p.Ile34Met (c.102C>G) is classified Uncertain significance in MAP2K7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-06). AlphaMissense: likely benign (0.1058); Ultra-rare (popmax 0.019%, afr).

How common is MAP2K7 p.Ile34Met (c.102C>G) in the general population?

MAP2K7 p.Ile34Met (c.102C>G) is ultra-rare (popmax 0.019%, afr) (gnomAD).

What do computational predictors say about MAP2K7 p.Ile34Met (c.102C>G)?

AlphaMissense predicts likely benign (score 0.1058) — an in-silico prediction, not a clinical call.

MAP2K7 p.Ile34Met

c.102C>G · VCV4051207

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1058 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.019%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1058	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -6.88	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 3.6	GERP 0.83, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 5,951 bp · p 0.32 · regional, not allelic
Overall
CADD	19.72	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 0.019% African / African-American · 13/68,412 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00883%

Overall 0.000932% 14/1,501,898 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.019%	5,262
Remaining individualsnot grpmax-eligible	0.00177%	56,466

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.Ile34Met
Coding: c.102C>G
MANE Select: NM_145185
Type: single nucleotide variant
Location: chr19:7904046 (GRCh38)
Gene constraint: LOEUF 0.454 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.94 · 37 PDB
Residue 34: the 'disordered' region

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-ile34met (accessed [today's date]).

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