Is MAPK11 p.Ala304Ser (c.910G>T) pathogenic?

MAPK11 p.Ala304Ser (c.910G>T) is classified Uncertain significance in MAPK11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). AlphaMissense: likely benign (0.0742); Absent from gnomAD v4.1.

How common is MAPK11 p.Ala304Ser (c.910G>T) in the general population?

MAPK11 p.Ala304Ser (c.910G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPK11 p.Ala304Ser (c.910G>T)?

AlphaMissense predicts likely benign (score 0.0742) — an in-silico prediction, not a clinical call.

MAPK11 p.Ala304Ser

c.910G>T · VCV3293185

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0742 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0742	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -6.69	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 4.8	GERP -2.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 5,341 bp · p 0.0083 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAPK11
Protein: p.Ala304Ser
Coding: c.910G>T
MANE Select: NM_002751
Type: single nucleotide variant
Location: chr22:50265426 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.88 · 4 PDB
Residue 304: the protein kinase domain

Full MAPK11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPK11 c.611-7C>T Benign ★★ same type
MAPK11 p.Ala121Ser Uncertain significance ★ ⚠ same type
MAPK11 p.Ala184Thr Uncertain significance ★ ⚠ same type
MAPK11 p.Arg189Gln Uncertain significance ★ ⚠ same type
MAPK11 p.Arg332His Uncertain significance ★ ⚠ same type
MAPK11 p.Arg45Trp Uncertain significance ★ ⚠ same type
MAPK11 p.Asp161Asn Uncertain significance ★ ⚠ same type
MAPK11 p.Asp176Glu 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/mapk11-p-ala304ser (accessed [today's date]).

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