Is MAPK15 p.Ser192Ter (c.575C>A) pathogenic?

MAPK15 p.Ser192Ter (c.575C>A) is classified Likely benign in MAPK15 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Rare (popmax 0.472%, afr).

How common is MAPK15 p.Ser192Ter (c.575C>A) in the general population?

MAPK15 p.Ser192Ter (c.575C>A) is rare (popmax 0.472%, afr) (gnomAD).

MAPK15 p.Ser192Ter

c.575C>A · rs151138393 · VCV787880

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.472%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 14
Splicing
SpliceAI	Δ0.21	donor gain · deltas
Pangolin	Δ0.22	gain · loss 0.15 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.1	GERP -0.23, phastCons 0.47
Overall
CADD	39.0	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 0.472% African / African-American · 343/72,652 alleles

Filtering AF 0.431% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.415%

Overall 0.029% 447/1,542,820 alleles · rare exomes 205/1,392,362 · genomes 242/150,458 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.472%	212
Admixed American	0.132%	756
Remaining individualsnot grpmax-eligible	0.0468%	2,136
Middle Eastern	0.0175%	5,718
East Asian	0.00491%	20,369
European (non-Finnish)	0.000612%	163,386

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.Ser192Ter
Coding: c.575C>A
MANE Select: NM_139021
dbSNP: rs151138393
Type: single nucleotide variant
Location: chr8:143719150 (GRCh38)
Gene constraint: LOEUF 1.344 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.56
Residue 192: the protein kinase domain

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

Similar variants

MAPK15 p.Arg496Trp Uncertain significance ★★ ⚠ 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
MAPK15 p.Ala436Val Uncertain significance ★ ⚠ same type
MAPK15 p.Ala514Thr 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-ser192ter (accessed [today's date]).

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