Is MAPKAPK2 p.Pro17= (c.51G>C) pathogenic?

MAPKAPK2 p.Pro17= (c.51G>C) is classified Likely benign in MAPKAPK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-12-20). Low-frequency (popmax 2.84%, nfe).

How common is MAPKAPK2 p.Pro17= (c.51G>C) in the general population?

MAPKAPK2 p.Pro17= (c.51G>C) is low-frequency (popmax 2.84%, nfe) (gnomAD).

MAPKAPK2 p.Pro17=

c.51G>C · rs1402681700 · VCV769547

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.84%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1	GERP -2.5, phastCons 0.95
Overall
CADD	9.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.84% European (non-Finnish) · 2,948/103,888 alleles

Filtering AF 2.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.72%

Overall 2.04% 4,107/201,546 alleles · low-frequency exomes 4,088/82,754 · genomes 19/118,792 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	3.7%	27
European (non-Finnish)grpmax	2.84%	35
Middle Eastern	2.8%	36
East Asian	2.44%	41
Finnishnot grpmax-eligible	2.25%	45
Ashkenazi Jewishnot grpmax-eligible	1.66%	60
South Asian	1.32%	76
Admixed American	0.494%	202
African / African-American	0.166%	604

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro17=
Coding: c.51G>C
MANE Select: NM_032960
dbSNP: rs1402681700
Type: single nucleotide variant
Location: chr1:206685280 (GRCh38)
Gene constraint: LOEUF 0.303 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.08 · 31 PDB
Residue 17: the 'disordered' region

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

Similar variants

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
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-pro17 (accessed [today's date]).

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