ALKBH8 p.Ser243=
c.729C>T · rs1048228218 · VCV2642352
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00477%, sas)
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 0.89 | GERP -2.6, phastCons 0.98 |
| Overall | ||
| CADD | 12.69 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00477%
South Asian · 4/83,898 alleles
Filtering AF
0.00161%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00095%
Overall
0.000774%
12/1,549,974 alleles · very rare
exomes 11/1,397,832 · genomes 1/152,142 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00477% | 20,975 |
| Remaining individualsnot grpmax-eligible | 0.00167% | 60,032 |
| European (non-Finnish) | 0.000611% | 163,694 |
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
- ALKBH8
- Protein
- p.Ser243=
- Coding
- c.729C>T
- MANE Select
- NM_138775
- dbSNP
- rs1048228218
- Type
- single nucleotide variant
- Location
- chr11:107549795 (GRCh38)
- Gene constraint
- LOEUF 0.797 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.91 · 3 PDB
- Residue 243
- the fe2og dioxygenase domain; a turn
Similar variants
- ALKBH8 p.Arg328Ter Pathogenic/Likely pathogenic ★★ same type
- ALKBH8 c.367+1G>T Uncertain significance ★★ same type
- ALKBH8 p.Ala367Asp Uncertain significance ★★ ⚠ same type
- ALKBH8 p.Arg277Gln Uncertain significance ★★ ⚠ same type
- ALKBH8 p.Arg369Trp Uncertain significance ★★ ⚠ same type
- ALKBH8 p.Arg481His Uncertain significance ★★ same type
- ALKBH8 p.Arg631His Uncertain significance ★★ ⚠ same type
- ALKBH8 p.Gln654Arg 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/alkbh8-p-ser243 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown