Is MAPK13 p.Glu192Lys (c.574G>A) pathogenic?

MAPK13 p.Glu192Lys (c.574G>A) is classified Uncertain significance in MAPK13 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-05). AlphaMissense: likely pathogenic (0.9913); Very rare (popmax 0.00891%, eas).

How common is MAPK13 p.Glu192Lys (c.574G>A) in the general population?

MAPK13 p.Glu192Lys (c.574G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about MAPK13 p.Glu192Lys (c.574G>A)?

AlphaMissense predicts likely pathogenic (score 0.9913) — an in-silico prediction, not a clinical call.

MAPK13 p.Glu192Lys

c.574G>A · rs762484290 · VCV2332795

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9913 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9913	likely pathogenic · top 9% in MAPK13
REVEL	0.703	pathogenic-leaning
SaProt	LLR -15.70	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 8,787 bp · p 0.59 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,894 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000929% 15/1,613,910 alleles · very rare exomes 12/1,461,680 · genomes 3/152,230 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,223
South Asian	0.00549%	18,211
Remaining individualsnot grpmax-eligible	0.0032%	31,236
European (non-Finnish)	0.000339%	294,993

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: MAPK13
Protein: p.Glu192Lys
Coding: c.574G>A
MANE Select: NM_002754
dbSNP: rs762484290
Type: single nucleotide variant
Location: chr6:36136734 (GRCh38)
Gene constraint: LOEUF 0.906 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.14 · 8 PDB
Residue 192: the protein kinase domain; an α-helix

Full MAPK13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPK13 p.Ala281Gly Uncertain significance ★ ⚠ same type
MAPK13 p.Ala302Thr Uncertain significance ★ ⚠ same type
MAPK13 p.Ala320Ser Uncertain significance ★ ⚠ same type
MAPK13 p.Arg276Trp Uncertain significance ★ ⚠ same type
MAPK13 p.Arg296His Uncertain significance ★ ⚠ same type
MAPK13 p.Arg354Gln Uncertain significance ★ ⚠ same type
MAPK13 p.Arg354Trp Uncertain significance ★ ⚠ same type
MAPK13 p.Arg358Trp 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/mapk13-p-glu192lys (accessed [today's date]).

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