Is MAP2K7 p.Val148Ile (c.442G>A) pathogenic?

MAP2K7 p.Val148Ile (c.442G>A) is classified Uncertain significance in MAP2K7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-25). AlphaMissense: likely benign (0.3352); Very rare (popmax 0.00334%, amr).

How common is MAP2K7 p.Val148Ile (c.442G>A) in the general population?

MAP2K7 p.Val148Ile (c.442G>A) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about MAP2K7 p.Val148Ile (c.442G>A)?

AlphaMissense predicts likely benign (score 0.3352) — an in-silico prediction, not a clinical call.

MAP2K7 p.Val148Ile

c.442G>A · VCV3870108

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3352 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3352	likely benign
REVEL	0.333	indeterminate
SaProt	LLR -11.97	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 1,458 bp · p 2.3e-17 · regional, not allelic
Overall
CADD	24.2	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 0.00334% Admixed American · 2/59,860 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00118% 19/1,611,932 alleles · very rare exomes 18/1,459,696 · genomes 1/152,236 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,930
African / African-American	0.00267%	37,453
Remaining individualsnot grpmax-eligible	0.0016%	62,406
European (non-Finnish)	0.0011%	90,729
South Asian	0.0011%	90,866

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.Val148Ile
Coding: c.442G>A
MANE Select: NM_145185
Type: single nucleotide variant
Location: chr19:7910368 (GRCh38)
Gene constraint: LOEUF 0.454 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.94 · 37 PDB
Residue 148: 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-val148ile (accessed [today's date]).

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