Is HDAC4 p.Arg465= (c.1395C>T) pathogenic?

HDAC4 p.Arg465= (c.1395C>T) is classified Likely benign in HDAC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-02). Rare (popmax 0.107%, eas).

How common is HDAC4 p.Arg465= (c.1395C>T) in the general population?

HDAC4 p.Arg465= (c.1395C>T) is rare (popmax 0.107%, eas) (gnomAD).

HDAC4 p.Arg465=

c.1395C>T · VCV4960829

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.107%, eas)

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 0.065	GERP -3.9, phastCons 0.75
Overall
CADD	7.011	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.107% East Asian · 48/44,880 alleles

Filtering AF 0.0829% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0743%

Overall 0.00335% 54/1,613,910 alleles · rare exomes 43/1,461,524 · genomes 11/152,386 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.107%	935
South Asian	0.00549%	18,216
Remaining individualsnot grpmax-eligible	0.0016%	62,494

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: HDAC4
Protein: p.Arg465=
Coding: c.1395C>T
MANE Select: NM_001378414
Type: single nucleotide variant
Location: chr2:239126594 (GRCh38)
Gene constraint: LOEUF 0.192 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 65.67 · 19 PDB

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

Similar variants

HDAC4 p.Arg465His Uncertain significance ★ ⚠ same residue
HDAC4 p.Pro248Leu Pathogenic ★★ same type
HDAC4 p.Thr244Lys Pathogenic/Likely pathogenic ★★ same type
HDAC4 c.865+8G>A Uncertain significance ★★ same type
HDAC4 p.Ala445Thr Uncertain significance ★★ ⚠ same type
HDAC4 p.Ala620Thr Uncertain significance ★★ ⚠ same type
HDAC4 p.Ala91Thr Uncertain significance ★★ ⚠ same type
HDAC4 p.Arg132Trp Uncertain significance ★★ ⚠ same type

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-arg465 (accessed [today's date]).

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