Is HDAC8 p.Cys102= (c.306C>T) pathogenic?

HDAC8 p.Cys102= (c.306C>T) is classified Likely benign in HDAC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-08). Absent from gnomAD v4.1; Associated with Cornelia de Lange syndrome 5.

What condition is associated with HDAC8 p.Cys102= (c.306C>T)?

HDAC8 p.Cys102= (c.306C>T) is associated with Cornelia de Lange syndrome 5 (ClinVar).

How common is HDAC8 p.Cys102= (c.306C>T) in the general population?

HDAC8 p.Cys102= (c.306C>T) is absent from gnomAD v4.1 (gnomAD).

HDAC8 p.Cys102=

c.306C>T · rs2522168228 · VCV2844198

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

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 2.9	GERP -0.13, phastCons 1
Overall
CADD	9.932	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: HDAC8
Protein: p.Cys102=
Coding: c.306C>T
MANE Select: NM_018486
dbSNP: rs2522168228
Type: single nucleotide variant
Location: chrX:72568020 (GRCh38)
Structure: AlphaFold pLDDT 95.45 · 53 PDB
Residue 102: the 'histone deacetylase' region; a β-strand

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

Disease context

Cornelia de Lange syndrome 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

HDAC8 p.Cys102Arg Uncertain significance ★ ⚠ same residue
HDAC8 p.Cys102Trp Uncertain significance ★ ⚠ same residue
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

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-cys102 (accessed [today's date]).

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