Is MAPK15 p.Arg115Pro (c.344G>C) pathogenic?

MAPK15 p.Arg115Pro (c.344G>C) is classified Uncertain significance in MAPK15 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-05). AlphaMissense: ambiguous (0.4947); Rare (popmax 0.129%, eas).

How common is MAPK15 p.Arg115Pro (c.344G>C) in the general population?

MAPK15 p.Arg115Pro (c.344G>C) is rare (popmax 0.129%, eas) (gnomAD).

What do computational predictors say about MAPK15 p.Arg115Pro (c.344G>C)?

AlphaMissense predicts ambiguous (score 0.4947) — an in-silico prediction, not a clinical call.

MAPK15 p.Arg115Pro

c.344G>C · rs782256408 · VCV2595339

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4947 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.129%, eas)

Computational evidence

Protein change
AlphaMissense	0.4947	ambiguous
REVEL	0.556	indeterminate
SaProt	LLR -13.91	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.2	GERP 2.1, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 5,870 bp · p 0.014 · regional, not allelic
Overall
CADD	25.5	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 0.129% East Asian · 58/44,806 alleles

Filtering AF 0.103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0932%

Overall 0.00465% 75/1,612,136 alleles · rare exomes 60/1,460,094 · genomes 15/152,042 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.129%	773
Remaining individualsnot grpmax-eligible	0.0208%	4,805
South Asian	0.0022%	45,470
European (non-Finnish)	0.00017%	589,859

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.Arg115Pro
Coding: c.344G>C
MANE Select: NM_139021
dbSNP: rs782256408
Type: single nucleotide variant
Location: chr8:143718832 (GRCh38)
Gene constraint: LOEUF 1.344 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.56
Residue 115: 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.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
MAPK15 p.Ala436Val 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-arg115pro (accessed [today's date]).

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