MAPK8 p.Gly35=
c.105A>G · rs777584404 · VCV759314
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0174%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 5.1 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 12.92 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0174%
Middle Eastern · 1/5,732 alleles
Filtering AF
0.00214%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00189%
Overall
0.00275%
42/1,525,990 alleles · ultra-rare
exomes 38/1,373,798 · genomes 4/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0174% | 5,732 |
| Remaining individualsnot grpmax-eligible | 0.0103% | 9,701 |
| European (non-Finnish) | 0.00297% | 33,616 |
| African / African-American | 0.00144% | 69,274 |
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.Gly35=
- Coding
- c.105A>G
- MANE Select
- NM_001323329
- dbSNP
- rs777584404
- Type
- single nucleotide variant
- Location
- chr10:48401765 (GRCh38)
- Gene constraint
- LOEUF 0.532 · pLI 0.95 (gnomAD)
- Structure
- AlphaFold pLDDT 83.75 · 41 PDB
- Residue 35
- the protein kinase domain; a binding site
Similar variants
- 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
- MAPK8 p.Trp352Ter 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/mapk8-p-gly35 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown