Is HDAC4 p.Thr697= (c.2091G>C) pathogenic?

HDAC4 p.Thr697= (c.2091G>C) is classified Likely benign in HDAC4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-17). Absent from gnomAD v4.1; Associated with HDAC4-related disorder.

What condition is associated with HDAC4 p.Thr697= (c.2091G>C)?

HDAC4 p.Thr697= (c.2091G>C) is associated with HDAC4-related disorder (ClinVar).

How common is HDAC4 p.Thr697= (c.2091G>C) in the general population?

HDAC4 p.Thr697= (c.2091G>C) is absent from gnomAD v4.1 (gnomAD).

HDAC4 p.Thr697=

c.2091G>C · rs993038179 · VCV3040945

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

HDAC4-related disorder

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 -14	GERP -5.2
Overall
CADD	0.066	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: HDAC4
Protein: p.Thr697=
Coding: c.2091G>C
MANE Select: NM_001378414
dbSNP: rs993038179
Type: single nucleotide variant
Location: chr2:239108071 (GRCh38)
Gene constraint: LOEUF 0.192 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 65.67 · 19 PDB
Residue 697: an α-helix; the 'histone deacetylase' region

Full HDAC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

HDAC4-related disorder

Similar variants

HDAC4 p.Thr697Met Uncertain significance ★ ⚠ same residue
HDAC4 p.Thr244Lys Pathogenic/Likely pathogenic ★★ same condition
HDAC4 p.Met49Val Uncertain significance ★★ ⚠ same condition
HDAC4 p.Pro16Ala Uncertain significance ★★ ⚠ same condition
HDAC4 p.Arg709Leu Uncertain significance ★ ⚠ same condition
HDAC4 p.Gln382Arg Uncertain significance ★ ⚠ same condition
HDAC4 p.Leu600Val Uncertain significance ★ ⚠ same condition
HDAC4 p.Leu998Met 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/hdac4-p-thr697 (accessed [today's date]).

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