Is HDAC8 p.Pro35fs (c.104_105del) pathogenic?

HDAC8 p.Pro35fs (c.104105del) is classified Pathogenic in HDAC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-03). No gnomAD frequency available for this variant; Associated with Cornelia de Lange syndrome 5.

What condition is associated with HDAC8 p.Pro35fs (c.104_105del)?

HDAC8 p.Pro35fs (c.104_105del) is associated with Cornelia de Lange syndrome 5 (ClinVar).

How common is HDAC8 p.Pro35fs (c.104_105del) in the general population?

HDAC8 p.Pro35fs (c.104_105del) is no gnomAD frequency available for this variant (gnomAD).

HDAC8 p.Pro35fs

c.104_105del · rs1556165162 · VCV545414

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Cornelia de Lange syndrome 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 1 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.6	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: HDAC8
Protein: p.Pro35fs
Coding: c.104_105del
MANE Select: NM_018486
dbSNP: rs1556165162
Type: Deletion
Location: chrX:72572657 (GRCh38)
Structure: AlphaFold pLDDT 95.45 · 53 PDB
Residue 35: 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.Pro35Leu Uncertain significance ★ ⚠ same residue
HDAC8 p.Pro35Thr Uncertain significance ★ ⚠ same residue
HDAC8 c.112-17del Benign ★★ same condition
HDAC8 c.(437+143_438-4 Pathogenic ★ same condition
HDAC8 p.Ala122fs Likely pathogenic ★ same condition
HDAC8 p.Glu250fs Pathogenic ★ same condition
HDAC8 p.Gly184fs Likely pathogenic ★ same condition
HDAC8 p.Ser43_Leu44insTer 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-pro35fs (accessed [today's date]).

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