MAPK8IP3 p.Ser564=
c.1692C>T · rs370939661 · VCV2578753
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0138%, nfe)
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 -1.3 | GERP -3.9, phastCons 0.002 |
| Overall | ||
| CADD | 7.325 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0138%
European (non-Finnish) · 159/1,153,080 alleles
Filtering AF
0.012%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0113%
Overall
0.0111%
173/1,564,260 alleles · ultra-rare
exomes 164/1,412,084 · genomes 9/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0138% | 7,252 |
| Remaining individualsnot grpmax-eligible | 0.0133% | 7,532 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0076% | 13,159 |
| Admixed American | 0.00548% | 18,243 |
| East Asian | 0.00225% | 44,352 |
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
- MAPK8IP3
- Protein
- p.Ser564=
- Coding
- c.1692C>T
- MANE Select
- NM_001318852
- dbSNP
- rs370939661
- Type
- single nucleotide variant
- Location
- chr16:1762696 (GRCh38)
- Gene constraint
- LOEUF 0.407 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 63.19 · 5 PDB
- Residue 564
- the rh2 domain; a UniProt-annotated variant site (in nedba)
Similar variants
- MAPK8IP3 p.Ser564Thr Uncertain significance ★ ⚠ same residue
- MAPK8IP3 p.Arg1147Cys Pathogenic/Likely pathogenic ★★ same type
- MAPK8IP3 p.Arg579Cys Pathogenic/Likely pathogenic ★★ same type
- MAPK8IP3 p.Gln468Ter Pathogenic/Likely pathogenic ★★ same type
- MAPK8IP3 p.Glu27Ter Likely pathogenic ★★ same type
- MAPK8IP3 p.Glu462Gly Likely pathogenic ★★ same type
- MAPK8IP3 p.Leu445Pro Likely pathogenic ★★ same type
- MAPK8IP3 p.Tyr37Ter Likely pathogenic ★★ 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/mapk8ip3-p-ser564 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown