Is MAPK8 p.Phe170= (c.510C>T) pathogenic?

MAPK8 p.Phe170= (c.510C>T) is classified Likely benign in MAPK8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-04-01). Ultra-rare (popmax 0.0571%, sas); Associated with MAPK8-related disorder.

What condition is associated with MAPK8 p.Phe170= (c.510C>T)?

MAPK8 p.Phe170= (c.510C>T) is associated with MAPK8-related disorder (ClinVar).

How common is MAPK8 p.Phe170= (c.510C>T) in the general population?

MAPK8 p.Phe170= (c.510C>T) is ultra-rare (popmax 0.0571%, sas) (gnomAD).

MAPK8 p.Phe170=

c.510C>T · rs199940599 · VCV3054629

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0571%, sas)

Conditions

MAPK8-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.92	GERP -0.48, phastCons 1
Overall
CADD	15.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0571% South Asian · 52/91,058 alleles

Filtering AF 0.0447% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0403%

Overall 0.0349% 563/1,613,610 alleles · ultra-rare exomes 539/1,461,506 · genomes 24/152,104 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0571%	1,751
European (non-Finnish)	0.0411%	2,432
Remaining individualsnot grpmax-eligible	0.0208%	4,805
Middle Eastern	0.0164%	6,080
African / African-American	0.0134%	7,488
East Asian	0.00223%	44,886
Admixed American	0.00167%	59,974

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: MAPK8
Protein: p.Phe170=
Coding: c.510C>T
MANE Select: NM_001323329
dbSNP: rs199940599
Type: single nucleotide variant
Location: chr10:48420214 (GRCh38)
Gene constraint: LOEUF 0.532 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 83.75 · 41 PDB
Residue 170: the protein kinase domain

Full MAPK8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MAPK8-related disorder

Similar variants

MAPK8 p.Gly16= Likely benign same condition
MAPK8 c.123-51A>C Benign ★★ same type
MAPK8 c.253-80T>A Benign ★★ same type
MAPK8 c.311+37A>G Benign ★★ same type
MAPK8 c.450+141T>G Benign ★★ same type
MAPK8 c.689-56T>A Benign ★★ same type
MAPK8 c.997-51T>A Benign ★★ same type
MAPK8 c.-49-77C>A Benign ★★ 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/mapk8-p-phe170 (accessed [today's date]).

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