HDAC8 p.Gln124=
c.372A>G · rs141306915 · VCV1164269
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00875%, afr)
Conditions
1
Cornelia de Lange syndrome 5
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 -0.82 | GERP -3.2, phastCons 0.01 |
| Overall | ||
| CADD | 3.372 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00875%
African / African-American · 5/57,152 alleles
Filtering AF
0.00339%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00215%
Overall
0.000744%
9/1,209,845 alleles · very rare
exomes 6/1,097,963 · genomes 3/111,882 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00875% | 11,430 |
| Admixed American | 0.00656% | 15,247 |
| South Asian | 0.00176% | 56,811 |
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
- HDAC8
- Protein
- p.Gln124=
- Coding
- c.372A>G
- MANE Select
- NM_018486
- dbSNP
- rs141306915
- Type
- single nucleotide variant
- Location
- chrX:72567954 (GRCh38)
- Structure
- AlphaFold pLDDT 95.45 · 53 PDB
- Residue 124
- the 'histone deacetylase' region; an α-helix
Similar variants
- HDAC8 c.165-2A>G Pathogenic ★★ same condition
- HDAC8 c.738-1G>A Pathogenic ★★ same condition
- HDAC8 c.738-2A>G Pathogenic/Likely pathogenic ★★ same condition
- HDAC8 p.Arg164Ter Pathogenic ★★ same condition
- HDAC8 p.Arg313Ter Pathogenic ★★ same condition
- HDAC8 p.Arg37Gln Pathogenic/Likely pathogenic ★★ same condition
- HDAC8 p.Asn156Ser Pathogenic ★★ same condition
- HDAC8 p.Gln263Ter Pathogenic ★★ same condition
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/hdac8-p-gln124 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown