Is HDAC8 p.Ile19= (c.57C>T) pathogenic?

HDAC8 p.Ile19= (c.57C>T) is classified Benign/Likely benign in HDAC8 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-09). Rare (popmax 0.419%, afr); Associated with Inborn genetic diseases.

What condition is associated with HDAC8 p.Ile19= (c.57C>T)?

HDAC8 p.Ile19= (c.57C>T) is associated with Inborn genetic diseases, Cornelia de Lange syndrome 5 (ClinVar).

How common is HDAC8 p.Ile19= (c.57C>T) in the general population?

HDAC8 p.Ile19= (c.57C>T) is rare (popmax 0.419%, afr) (gnomAD).

HDAC8 p.Ile19=

c.57C>T · rs145362166 · VCV1301021

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.419%, afr)

Conditions

Inborn genetic diseases

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 2.8	GERP 0.38, phastCons 1
Overall
CADD	11.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.419% African / African-American · 228/54,478 alleles

Filtering AF 0.374% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.357%

Overall 0.024% 285/1,185,040 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.419%	239
Admixed American	0.0522%	1,916
Remaining individualsnot grpmax-eligible	0.0519%	1,926
European (non-Finnish)	0.00113%	88,147

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.Ile19=
Coding: c.57C>T
MANE Select: NM_018486
dbSNP: rs145362166
Type: single nucleotide variant
Location: chrX:72572705 (GRCh38)
Structure: AlphaFold pLDDT 95.45 · 53 PDB
Residue 19: the 'histone deacetylase' region; a β-strand

Full HDAC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Cornelia de Lange syndrome 5

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.Arg166Ter Pathogenic ★★ same condition
HDAC8 p.Arg313Ter Pathogenic ★★ same condition
HDAC8 p.Arg37Gln Pathogenic/Likely pathogenic ★★ same condition
HDAC8 p.Asn156Ser 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-ile19 (accessed [today's date]).

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