Is MAPKAPK3 p.Ala27Pro (c.79G>C) pathogenic?

MAPKAPK3 p.Ala27Pro (c.79G>C) is classified Uncertain significance in MAPKAPK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: likely benign (0.0556); Very rare (popmax 0.0033%, sas).

How common is MAPKAPK3 p.Ala27Pro (c.79G>C) in the general population?

MAPKAPK3 p.Ala27Pro (c.79G>C) is very rare (popmax 0.0033%, sas) (gnomAD).

What do computational predictors say about MAPKAPK3 p.Ala27Pro (c.79G>C)?

AlphaMissense predicts likely benign (score 0.0556) — an in-silico prediction, not a clinical call.

MAPKAPK3 p.Ala27Pro

c.79G>C · VCV4780349

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0556 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0556	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -6.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -1, phastCons 0.74
Regional constraint	o/e 1.04	unconstrained · MANE · 23 kb · p 0.63 · regional, not allelic
Overall
CADD	16.59	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 0.0033% South Asian · 3/91,012 alleles

Filtering AF 0.000876% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000186% 3/1,609,652 alleles · very rare exomes 3/1,457,292 · genomes 0/152,360 · joint denominator

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: MAPKAPK3
Protein: p.Ala27Pro
Coding: c.79G>C
MANE Select: NM_001243925
Type: single nucleotide variant
Location: chr3:50617644 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.10 · 5 PDB
Residue 27: the 'disordered' region

Full MAPKAPK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPKAPK3 p.Ala181Ser Uncertain significance ★★ ⚠ same type
MAPKAPK3 p.Arg112His Uncertain significance ★★ ⚠ same type
MAPKAPK3 p.Arg148Gln Uncertain significance ★★ ⚠ same type
MAPKAPK3 p.Arg148Trp Uncertain significance ★★ ⚠ same type
MAPKAPK3 p.Arg259Cys Uncertain significance ★★ same type
MAPKAPK3 p.Arg282Cys Uncertain significance ★★ ⚠ same type
MAPKAPK3 p.Arg282His Uncertain significance ★★ ⚠ same type
MAPKAPK3 p.Arg319Gln 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/mapkapk3-p-ala27pro (accessed [today's date]).

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