Is MAPKAPK3 p.Pro34Ser (c.100C>T) pathogenic?

MAPKAPK3 p.Pro34Ser (c.100C>T) is classified Uncertain significance in MAPKAPK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-09). AlphaMissense: ambiguous (0.3418); Absent from gnomAD v4.1.

How common is MAPKAPK3 p.Pro34Ser (c.100C>T) in the general population?

MAPKAPK3 p.Pro34Ser (c.100C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPKAPK3 p.Pro34Ser (c.100C>T)?

AlphaMissense predicts ambiguous (score 0.3418) — an in-silico prediction, not a clinical call.

MAPKAPK3 p.Pro34Ser

c.100C>T · VCV4716973

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3418 · 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	0.3418	ambiguous
REVEL	0.063	moderately benign-leaning
SaProt	LLR -11.13	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 4.7	GERP 2.6, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 23 kb · p 0.63 · regional, not allelic
Overall
CADD	24.1	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: MAPKAPK3
Protein: p.Pro34Ser
Coding: c.100C>T
MANE Select: NM_001243925
Type: single nucleotide variant
Location: chr3:50617665 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.10 · 5 PDB
Residue 34: the 'disordered' region

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

Similar variants

MAPKAPK3 p.Pro34= Likely benign ★ same residue
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

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-pro34ser (accessed [today's date]).

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