Is MAPK14 p.Arg10Pro (c.29G>C) pathogenic?

MAPK14 p.Arg10Pro (c.29G>C) is classified Uncertain significance in MAPK14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely pathogenic (0.9068); Very rare (popmax 0.000424%, nfe).

How common is MAPK14 p.Arg10Pro (c.29G>C) in the general population?

MAPK14 p.Arg10Pro (c.29G>C) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about MAPK14 p.Arg10Pro (c.29G>C)?

AlphaMissense predicts likely pathogenic (score 0.9068) — an in-silico prediction, not a clinical call.

MAPK14 p.Arg10Pro

c.29G>C · VCV4103755

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9068 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9068	likely pathogenic
REVEL	0.258	benign-leaning
SaProt	LLR -14.81	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	Δ0.37	acceptor gain · deltas
Pangolin	Δ0.46	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5	GERP 4.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 85 bp · p 0.47 · regional, not allelic
Overall
CADD	34.0	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

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,698 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,630 alleles · very rare exomes 5/1,461,302 · genomes 0/152,328 · 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: MAPK14
Protein: p.Arg10Pro
Coding: c.29G>C
MANE Select: NM_139012
Type: single nucleotide variant
Location: chr6:36028186 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 89.91 · 267 PDB
Residue 10: a β-strand

Full MAPK14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPK14 p.Arg10Trp Uncertain significance ★ ⚠ same residue
MAPK14 c.763-2308A>G Uncertain significance ★ same type
MAPK14 c.763-2312A>G Uncertain significance ★ same type
MAPK14 c.763-2316G>A Uncertain significance ★ same type
MAPK14 c.763-2341C>G Uncertain significance ★ same type
MAPK14 c.763-2356G>A Uncertain significance ★ same type
MAPK14 p.Ala304Val Uncertain significance ★ ⚠ same type
MAPK14 p.Ala41Thr 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/mapk14-p-arg10pro (accessed [today's date]).

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