Is MAPK15 p.Val199fs (c.596_606del) pathogenic?

MAPK15 p.Val199fs (c.596606del) is classified Uncertain significance in MAPK15 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-11). Rare (popmax 0.174%, afr).

How common is MAPK15 p.Val199fs (c.596_606del) in the general population?

MAPK15 p.Val199fs (c.596_606del) is rare (popmax 0.174%, afr) (gnomAD).

MAPK15 p.Val199fs

c.596_606del · VCV4901738

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.174%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP -2.2, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.174% African / African-American · 130/74,910 alleles

Filtering AF 0.149% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.14%

Overall 0.00839% 135/1,608,106 alleles · rare exomes 60/1,455,784 · genomes 75/152,322 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.174%	576
Remaining individualsnot grpmax-eligible	0.00643%	15,553
Admixed American	0.00169%	59,266

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.Val199fs
Coding: c.596_606del
MANE Select: NM_139021
Type: Deletion
Location: chr8:143719355 (GRCh38)
Gene constraint: LOEUF 1.344 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.56
Residue 199: the protein kinase domain

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

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-val199fs (accessed [today's date]).

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