Is MAPK15 p.Ala373Pro (c.1117G>C) pathogenic?

MAPK15 p.Ala373Pro (c.1117G>C) is classified Likely benign in MAPK15 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). AlphaMissense: likely benign (0.0705); Low-frequency (popmax 1.52%, mid).

How common is MAPK15 p.Ala373Pro (c.1117G>C) in the general population?

MAPK15 p.Ala373Pro (c.1117G>C) is low-frequency (popmax 1.52%, mid) (gnomAD).

What do computational predictors say about MAPK15 p.Ala373Pro (c.1117G>C)?

AlphaMissense predicts likely benign (score 0.0705) — an in-silico prediction, not a clinical call.

MAPK15 p.Ala373Pro

c.1117G>C · rs140439631 · VCV2658906

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0705 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.52%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0705	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -5.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP -1.3, phastCons 0.002
Regional constraint	o/e 1.09	unconstrained · MANE · 5,870 bp · p 0.014 · regional, not allelic
Overall
CADD	11.5	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 1.52% Middle Eastern · 92/6,058 alleles

Filtering AF 1.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.17%

Overall 0.131% 2,122/1,613,716 alleles · low-frequency exomes 1,921/1,461,462 · genomes 201/152,254 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	3.19%	31
Middle Easterngrpmax	1.52%	66
Remaining individualsnot grpmax-eligible	0.288%	347
South Asian	0.133%	753
Admixed American	0.085%	1,177
European (non-Finnish)	0.0606%	1,650
African / African-American	0.024%	4,168

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala373Pro
Coding: c.1117G>C
MANE Select: NM_139021
dbSNP: rs140439631
Type: single nucleotide variant
Location: chr8:143721324 (GRCh38)
Gene constraint: LOEUF 1.344 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.56
Residue 373: the 'requires for interaction with gabarap, map1lc3b and gabarapl1' region; the 'disordered' region

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-ala373pro (accessed [today's date]).

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