Is MAPKAPK2 p.Ala111Val (c.332C>T) pathogenic?

MAPKAPK2 p.Ala111Val (c.332C>T) is classified Uncertain significance in MAPKAPK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: ambiguous (0.4505); Absent from gnomAD v4.1.

How common is MAPKAPK2 p.Ala111Val (c.332C>T) in the general population?

MAPKAPK2 p.Ala111Val (c.332C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPKAPK2 p.Ala111Val (c.332C>T)?

AlphaMissense predicts ambiguous (score 0.4505) — an in-silico prediction, not a clinical call.

MAPKAPK2 p.Ala111Val

c.332C>T · rs782185154 · VCV3123350

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4505 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4505	ambiguous
REVEL	0.272	benign-leaning
SaProt	LLR -12.03	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 45 kb · p 2.9e-09 · regional, not allelic
Overall
CADD	23.6	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

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: MAPKAPK2
Protein: p.Ala111Val
Coding: c.332C>T
MANE Select: NM_032960
dbSNP: rs782185154
Type: single nucleotide variant
Location: chr1:206728762 (GRCh38)
Gene constraint: LOEUF 0.303 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.08 · 31 PDB
Residue 111: the protein kinase domain; an α-helix

Full MAPKAPK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPKAPK2 p.Pro17= Likely benign ★★ same type
MAPKAPK2 p.Thr66= Benign ★★ same type
MAPKAPK2 p.Ala33Gly Uncertain significance ★ ⚠ same type
MAPKAPK2 p.Ala378Gly Uncertain significance ★ ⚠ same type
MAPKAPK2 p.Ala390Thr Uncertain significance ★ ⚠ same type
MAPKAPK2 p.Arg110Trp Uncertain significance ★ ⚠ same type
MAPKAPK2 p.Arg119Gln Uncertain significance ★ ⚠ same type
MAPKAPK2 p.Arg149Ter 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/mapkapk2-p-ala111val (accessed [today's date]).

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