Is MAPK3 p.Ser159= (c.477C>T) pathogenic?

MAPK3 p.Ser159= (c.477C>T) is classified Likely benign in MAPK3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-22). Ultra-rare (popmax 0.088%, eas); Associated with MAPK3-related disorder.

What condition is associated with MAPK3 p.Ser159= (c.477C>T)?

MAPK3 p.Ser159= (c.477C>T) is associated with MAPK3-related disorder (ClinVar).

How common is MAPK3 p.Ser159= (c.477C>T) in the general population?

MAPK3 p.Ser159= (c.477C>T) is ultra-rare (popmax 0.088%, eas) (gnomAD).

MAPK3 p.Ser159=

c.477C>T · rs142560490 · VCV3047898

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.088%, eas)

Conditions

MAPK3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.115	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -3.9
Overall
CADD	0.409	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.088% East Asian · 39/44,328 alleles

Filtering AF 0.0661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0585%

Overall 0.0193% 308/1,599,700 alleles · ultra-rare exomes 270/1,461,662 · genomes 38/138,038 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.088%	1,137
Admixed American	0.0408%	2,450
Remaining individualsnot grpmax-eligible	0.0209%	4,789
European (non-Finnish)	0.0179%	5,591
South Asian	0.0177%	5,650
African / African-American	0.0057%	17,531
Finnishnot grpmax-eligible	0.00315%	31,741

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.Ser159=
Coding: c.477C>T
MANE Select: NM_002746
dbSNP: rs142560490
Type: single nucleotide variant
Location: chr16:30118415 (GRCh38)
Gene constraint: LOEUF 0.935 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.09 · 8 PDB
Residue 159: the protein kinase domain; an α-helix

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

Disease context

MAPK3-related disorder

Similar variants

MAPK3 p.Tyr42Ter Uncertain significance ★ same condition
MAPK3 c.1017+48G>A Benign same condition
MAPK3 p.Gly23= Likely benign same condition
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.Arg15Ser 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-ser159 (accessed [today's date]).

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