Is MAPK13 p.Pro93Ser (c.277C>T) pathogenic?

MAPK13 p.Pro93Ser (c.277C>T) is classified Uncertain significance in MAPK13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.2654); Ultra-rare (popmax 0.0148%, nfe).

How common is MAPK13 p.Pro93Ser (c.277C>T) in the general population?

MAPK13 p.Pro93Ser (c.277C>T) is ultra-rare (popmax 0.0148%, nfe) (gnomAD).

What do computational predictors say about MAPK13 p.Pro93Ser (c.277C>T)?

AlphaMissense predicts likely benign (score 0.2654) — an in-silico prediction, not a clinical call.

MAPK13 p.Pro93Ser

c.277C>T · rs748450780 · VCV2356627

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2654 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0148%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2654	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -10.68	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.094	phastCons 0.003
Regional constraint	o/e 0.98	unconstrained · MANE · 8,787 bp · p 0.59 · regional, not allelic
Overall
CADD	13.01	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 0.0148% European (non-Finnish) · 175/1,180,050 alleles

Filtering AF 0.013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0123%

Overall 0.0113% 182/1,614,108 alleles · ultra-rare exomes 172/1,461,878 · genomes 10/152,230 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0148%	6,743
Remaining individualsnot grpmax-eligible	0.0064%	15,622
African / African-American	0.004%	24,978

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.Pro93Ser
Coding: c.277C>T
MANE Select: NM_002754
dbSNP: rs748450780
Type: single nucleotide variant
Location: chr6:36132648 (GRCh38)
Gene constraint: LOEUF 0.906 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.14 · 8 PDB
Residue 93: the protein kinase domain

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-pro93ser (accessed [today's date]).

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