Is MAPKAPK2 p.Pro32Ala (c.94C>G) pathogenic?

MAPKAPK2 p.Pro32Ala (c.94C>G) is classified Uncertain significance in MAPKAPK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-11). AlphaMissense: likely benign (0.0543); Ultra-rare (popmax 0.016%, nfe).

How common is MAPKAPK2 p.Pro32Ala (c.94C>G) in the general population?

MAPKAPK2 p.Pro32Ala (c.94C>G) is ultra-rare (popmax 0.016%, nfe) (gnomAD).

What do computational predictors say about MAPKAPK2 p.Pro32Ala (c.94C>G)?

AlphaMissense predicts likely benign (score 0.0543) — an in-silico prediction, not a clinical call.

MAPKAPK2 p.Pro32Ala

c.94C>G · VCV3543214

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0543 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0543	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -7.71	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 1.8	GERP 0.58, phastCons 0.01
Regional constraint	o/e 1.15	unconstrained · MANE · 232 bp · p 0.18 · regional, not allelic
Overall
CADD	13.59	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

Grpmax group 0.016% European (non-Finnish) · 171/1,068,898 alleles

Filtering AF 0.014% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0133%

Overall 0.0132% 187/1,419,704 alleles · ultra-rare exomes 172/1,271,368 · genomes 15/148,336 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.016%	6,251
Remaining individualsnot grpmax-eligible	0.0155%	6,456
Finnishnot grpmax-eligible	0.00926%	10,798
African / African-American	0.00453%	22,052

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: MAPKAPK2
Protein: p.Pro32Ala
Coding: c.94C>G
MANE Select: NM_032960
Type: single nucleotide variant
Location: chr1:206685323 (GRCh38)
Gene constraint: LOEUF 0.303 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.08 · 31 PDB
Residue 32: the 'disordered' region

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

Similar variants

MAPKAPK2 p.Pro32Leu Uncertain significance ★ ⚠ same residue
MAPKAPK2 p.Pro17= Likely benign ★★ same type
MAPKAPK2 p.Thr66= Benign ★★ same type
MAPKAPK2 p.Ala111Val Uncertain significance ★ ⚠ 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

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-pro32ala (accessed [today's date]).

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