Is MAPK3 p.Arg15Cys (c.43C>T) pathogenic?

MAPK3 p.Arg15Cys (c.43C>T) is classified Likely benign in MAPK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.2376); Rare (popmax 0.216%, amr).

How common is MAPK3 p.Arg15Cys (c.43C>T) in the general population?

MAPK3 p.Arg15Cys (c.43C>T) is rare (popmax 0.216%, amr) (gnomAD).

What do computational predictors say about MAPK3 p.Arg15Cys (c.43C>T)?

AlphaMissense predicts likely benign (score 0.2376) — an in-silico prediction, not a clinical call.

MAPK3 p.Arg15Cys

c.43C>T · rs766922585 · VCV720009

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2376 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.216%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2376	likely benign
REVEL	0.338	indeterminate
SaProt	LLR -8.87	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP -0.78, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 1,297 bp · p 0.3 · regional, not allelic
Overall
CADD	23.8	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 0.216% Admixed American · 90/41,630 alleles

Filtering AF 0.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.167%

Overall 0.00662% 94/1,420,482 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.216%	463
European (non-Finnish)	0.000375%	266,332

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: MAPK3
Protein: p.Arg15Cys
Coding: c.43C>T
MANE Select: NM_002746
dbSNP: rs766922585
Type: single nucleotide variant
Location: chr16:30123167 (GRCh38)
Gene constraint: LOEUF 0.935 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.09 · 8 PDB
Residue 15: the 'disordered' region

Full MAPK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPK3 p.Arg15Ser Uncertain significance ★ ⚠ same residue
MAPK3 p.Gly11= Likely benign ★★ same type
MAPK3 p.Pro336= Benign/Likely benign ★★ same type
MAPK3 p.Tyr148Cys Likely pathogenic ★ same type
MAPK3 p.Ala378Asp Uncertain significance ★ ⚠ same type
MAPK3 p.Arg242Gln Uncertain significance ★ ⚠ same type
MAPK3 p.Arg309Gln Uncertain significance ★ ⚠ same type
MAPK3 p.Arg309Gly 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/mapk3-p-arg15cys (accessed [today's date]).

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