Is MAPK10 p.Ala320= (c.960G>A) pathogenic?

MAPK10 p.Ala320= (c.960G>A) is classified Benign in MAPK10 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2019-12-31). Common (popmax 10%, eas) — too common for a highly-penetrant pathogenic allele.

MAPK10 p.Ala320=

Q: How common is MAPK10 p.Ala320= (c.960G>A) in the general population?

MAPK10 p.Ala320= (c.960G>A) is common (popmax 10%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.960G>A · rs55663953 · VCV129587

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 10%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.18	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.8	GERP -5.7
Overall
CADD	11.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10% East Asian · 4,491/44,870 alleles

Filtering AF 9.76% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.66%

Overall 0.401% 6,475/1,612,814 alleles · common exomes 5,796/1,460,642 · genomes 679/152,172 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	10%	10
Remaining individualsnot grpmax-eligible	0.578%	173
African / African-American	0.125%	798
European (non-Finnish)	0.114%	878
South Asian	0.109%	918
Ashkenazi Jewishnot grpmax-eligible	0.0982%	1,018
Finnishnot grpmax-eligible	0.0516%	1,938
Admixed American	0.0401%	2,495
Middle Eastern	0.0165%	6,056

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: MAPK10
Protein: p.Ala320=
Coding: c.960G>A
MANE Select: NM_138982
dbSNP: rs55663953
Type: single nucleotide variant
Location: chr4:86067798 (GRCh38)
Gene constraint: LOEUF 0.54 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 80.50 · 65 PDB
Residue 320: the protein kinase domain

Full MAPK10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPK10 p.Asp351= Benign ★★ same type
MAPK10 p.Val113= Benign/Likely benign ★★ same type
MAPK10 p.Ala353Thr Uncertain significance ★ ⚠ same type
MAPK10 p.Asn89Ser Uncertain significance ★ ⚠ same type
MAPK10 p.Asp141Glu Uncertain significance ★ ⚠ same type
MAPK10 p.Asp267Gly Uncertain significance ★ ⚠ same type
MAPK10 p.Asp315Asn Uncertain significance ★ same type
MAPK10 p.Cys79Gly 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/mapk10-p-ala320 (accessed [today's date]).

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