Is MAPKAPK2 p.Arg110Trp (c.328C>T) pathogenic?

MAPKAPK2 p.Arg110Trp (c.328C>T) is classified Uncertain significance in MAPKAPK2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-05-05). AlphaMissense: likely pathogenic (0.8135); Ultra-rare (popmax 0.0312%, eas).

How common is MAPKAPK2 p.Arg110Trp (c.328C>T) in the general population?

MAPKAPK2 p.Arg110Trp (c.328C>T) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

What do computational predictors say about MAPKAPK2 p.Arg110Trp (c.328C>T)?

AlphaMissense predicts likely pathogenic (score 0.8135) — an in-silico prediction, not a clinical call.

MAPKAPK2 p.Arg110Trp

c.328C>T · rs375800332 · VCV2454751

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8135 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8135	likely pathogenic
REVEL	0.719	pathogenic-leaning
SaProt	LLR -14.27	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -1.5, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 45 kb · p 2.9e-09 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0312% East Asian · 14/44,896 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.00477% 77/1,613,726 alleles · ultra-rare exomes 69/1,461,514 · genomes 8/152,212 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0312%	3,207
Remaining individualsnot grpmax-eligible	0.0128%	7,808
South Asian	0.00988%	10,121
European (non-Finnish)	0.0039%	25,651

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.Arg110Trp
Coding: c.328C>T
MANE Select: NM_032960
dbSNP: rs375800332
Type: single nucleotide variant
Location: chr1:206728758 (GRCh38)
Gene constraint: LOEUF 0.303 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.08 · 31 PDB
Residue 110: 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.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.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-arg110trp (accessed [today's date]).

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