Is HDAC8 p.Val15= (c.45C>G) pathogenic?

HDAC8 p.Val15= (c.45C>G) is classified Likely benign in HDAC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-27). Very rare (popmax 0.00357%, afr); Associated with Cornelia de Lange syndrome 5.

What condition is associated with HDAC8 p.Val15= (c.45C>G)?

HDAC8 p.Val15= (c.45C>G) is associated with Cornelia de Lange syndrome 5 (ClinVar).

How common is HDAC8 p.Val15= (c.45C>G) in the general population?

HDAC8 p.Val15= (c.45C>G) is very rare (popmax 0.00357%, afr) (gnomAD).

HDAC8 p.Val15=

c.45C>G · VCV3719993

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00357%, afr)

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	<0.2	all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.9	GERP -1.1, phastCons 1
Overall
CADD	7.368	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00357% African / African-American · 2/56,095 alleles

Filtering AF 0.000591% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000221%

Overall 0.00184% 2/108,873 alleles · very rare

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.Val15=
Coding: c.45C>G
MANE Select: NM_018486
Type: single nucleotide variant
Location: chrX:72572717 (GRCh38)
Structure: AlphaFold pLDDT 95.45 · 53 PDB
Residue 15: the 'histone deacetylase' region

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.Val15Ile 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
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-val15 (accessed [today's date]).

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