Is MAPKAPK3 p.Pro311Ser (c.931C>T) pathogenic?

MAPKAPK3 p.Pro311Ser (c.931C>T) is classified Uncertain significance in MAPKAPK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-11). AlphaMissense: likely pathogenic (0.7757); No allele count reported in gnomAD v4.1 (AN 1,589,186).

How common is MAPKAPK3 p.Pro311Ser (c.931C>T) in the general population?

MAPKAPK3 p.Pro311Ser (c.931C>T) is no allele count reported in gnomAD v4.1 (AN 1,589,186) (gnomAD).

What do computational predictors say about MAPKAPK3 p.Pro311Ser (c.931C>T)?

AlphaMissense predicts likely pathogenic (score 0.7757) — an in-silico prediction, not a clinical call.

MAPKAPK3 p.Pro311Ser

c.931C>T · rs2107603341 · VCV1501829

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7757 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,589,186)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7757	likely pathogenic
REVEL	0.435	indeterminate
SaProt	LLR -9.39	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 1,880 bp · p 0.058 · regional, not allelic
Overall
CADD	28.7	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

No allele count reported in gnomAD v4.1 (AN 1,589,186). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MAPKAPK3
Protein: p.Pro311Ser
Coding: c.931C>T
MANE Select: NM_001243925
dbSNP: rs2107603341
Type: single nucleotide variant
Location: chr3:50647138 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.10 · 5 PDB
Residue 311: the 'autoinhibitory helix' region

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

Similar variants

MAPKAPK3 p.Pro311Leu Uncertain significance ★ ⚠ 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-pro311ser (accessed [today's date]).

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