Is HDAC8 p.Asp213= (c.639C>T) pathogenic?

HDAC8 p.Asp213= (c.639C>T) is classified Benign/Likely benign in HDAC8 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-15). Rare (popmax 0.171%, sas); Associated with Inborn genetic diseases.

What condition is associated with HDAC8 p.Asp213= (c.639C>T)?

HDAC8 p.Asp213= (c.639C>T) is associated with Inborn genetic diseases, Cornelia de Lange syndrome 5 (ClinVar).

How common is HDAC8 p.Asp213= (c.639C>T) in the general population?

HDAC8 p.Asp213= (c.639C>T) is rare (popmax 0.171%, sas) (gnomAD).

HDAC8 p.Asp213=

c.639C>T · rs142540077 · VCV724622

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.171%, sas)

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 0.19	GERP -5.2
Overall
CADD	1.549	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.171% South Asian · 90/52,711 alleles

Filtering AF 0.142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.132%

Overall 0.0199% 234/1,176,345 alleles · rare exomes 226/1,070,126 · genomes 8/106,219 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.171%	586
Middle Eastern	0.0701%	1,427
European (non-Finnish)	0.0147%	6,818
Admixed American	0.0137%	7,322
Remaining individualsnot grpmax-eligible	0.0129%	7,756
African / African-American	0.00182%	54,944

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.Asp213=
Coding: c.639C>T
MANE Select: NM_018486
dbSNP: rs142540077
Type: single nucleotide variant
Location: chrX:72489031 (GRCh38)
Structure: AlphaFold pLDDT 95.45 · 53 PDB
Residue 213: the 'histone deacetylase' region

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-asp213 (accessed [today's date]).

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