Is MAPK15 p.Val151Met (c.451G>A) pathogenic?

MAPK15 p.Val151Met (c.451G>A) is classified Uncertain significance in MAPK15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-11). AlphaMissense: likely benign (0.3374); Very rare (popmax 0.0017%, nfe).

How common is MAPK15 p.Val151Met (c.451G>A) in the general population?

MAPK15 p.Val151Met (c.451G>A) is very rare (popmax 0.0017%, nfe) (gnomAD).

What do computational predictors say about MAPK15 p.Val151Met (c.451G>A)?

AlphaMissense predicts likely benign (score 0.3374) — an in-silico prediction, not a clinical call.

MAPK15 p.Val151Met

c.451G>A · VCV3870427

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3374 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0017%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3374	likely benign
REVEL	0.379	indeterminate
SaProt	LLR -12.98	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.4	GERP -0.39, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 5,870 bp · p 0.014 · regional, not allelic
Overall
CADD	23.7	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 0.0017% European (non-Finnish) · 20/1,176,156 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000903%

Overall 0.00131% 21/1,604,246 alleles · very rare exomes 18/1,452,040 · genomes 3/152,206 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0017%	58,808
Remaining individualsnot grpmax-eligible	0.00161%	62,100

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: MAPK15
Protein: p.Val151Met
Coding: c.451G>A
MANE Select: NM_139021
Type: single nucleotide variant
Location: chr8:143719026 (GRCh38)
Gene constraint: LOEUF 1.344 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.56
Residue 151: the protein kinase domain

Full MAPK15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPK15 p.Val151Leu Uncertain significance ★ ⚠ same residue
MAPK15 p.Arg496Trp Uncertain significance ★★ ⚠ same type
MAPK15 p.Ser192Ter Likely benign ★★ same type
MAPK15 p.Ala179Thr Uncertain significance ★ ⚠ same type
MAPK15 p.Ala251Val Uncertain significance ★ ⚠ same type
MAPK15 p.Ala295Thr Uncertain significance ★ ⚠ same type
MAPK15 p.Ala40Val Uncertain significance ★ ⚠ same type
MAPK15 p.Ala436Ser 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/mapk15-p-val151met (accessed [today's date]).

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