Is HDAC6 p.Val69fs (c.206_209del) pathogenic?

HDAC6 p.Val69fs (c.206209del) is classified Pathogenic in HDAC6 (ClinVar, No assertion criteria, 1 submitter). Absent from gnomAD; Associated with X-linked dominant chondrodysplasia, Chassaing-Lacombe type.

What condition is associated with HDAC6 p.Val69fs (c.206_209del)?

HDAC6 p.Val69fs (c.206_209del) is associated with X-linked dominant chondrodysplasia, Chassaing-Lacombe type (ClinVar).

How common is HDAC6 p.Val69fs (c.206_209del) in the general population?

HDAC6 p.Val69fs (c.206_209del) is absent from gnomAD (gnomAD).

HDAC6 p.Val69fs

Q: How is X-linked dominant chondrodysplasia, Chassaing-Lacombe type inherited?

Typically X-linked dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.206_209del · rs2519366970 · VCV3248614

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

X-linked dominant chondrodysplasia, Chassaing-Lacombe type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.72	GERP 0.75, phastCons 0.21

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: HDAC6
Protein: p.Val69fs
Coding: c.206_209del
MANE Select: NM_006044
dbSNP: rs2519366970
Type: Deletion
Location: chrX:48802982 (GRCh38)
Structure: AlphaFold pLDDT 77.66 · 22 PDB

Full HDAC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

X-linked dominant chondrodysplasia, Chassaing-Lacombe type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked dominant chondrodysplasia, Chassaing-Lacombe type (Orphanet):

Inheritance: X-linked dominant
Onset: Infancy, Neonatal

Similar variants

HDAC6 c.2187+20G>A Benign ★★ same condition
HDAC6 p.Ile929Thr Benign/Likely benign ★★ same condition
HDAC6 p.Thr1034Ala Likely benign ★★ same condition
HDAC6 p.Tyr171= Benign/Likely benign ★★ same condition
HDAC6 p.His632Tyr Likely pathogenic ★ ⚠ same condition
HDAC6 p.Gly1064Arg Uncertain significance ★ ⚠ same condition
HDAC6 p.Leu59Pro Conflicting classifications of pathogenicity ★ ⚠ same condition
HDAC6 p.Thr697Ile Uncertain significance ★ ⚠ 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/hdac6-p-val69fs (accessed [today's date]).

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