Is HDAC6 p.Phe264= (c.792C>T) pathogenic?

HDAC6 p.Phe264= (c.792C>T) is classified Likely benign in HDAC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-17). Very rare (popmax 0.0018%, nfe).

How common is HDAC6 p.Phe264= (c.792C>T) in the general population?

HDAC6 p.Phe264= (c.792C>T) is very rare (popmax 0.0018%, nfe) (gnomAD).

HDAC6 p.Phe264=

c.792C>T · VCV4950432

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0018%, nfe)

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 · C>A here scores Δ0.30 · evaluated, not missing
Pangolin	Δ0.23	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP -0.34	GERP -3.8, phastCons 0.3
Overall
CADD	8.657	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0018% European (non-Finnish) · 16/887,986 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000863%

Overall 0.00317% 38/1,199,459 alleles · very rare exomes 31/1,088,136 · genomes 7/111,323 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0477%	2,098
European (non-Finnish)grpmax	0.0018%	55,499

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: HDAC6
Protein: p.Phe264=
Coding: c.792C>T
MANE Select: NM_006044
Type: single nucleotide variant
Location: chrX:48808312 (GRCh38)
Structure: AlphaFold pLDDT 77.66 · 22 PDB
Residue 264: the 'histone deacetylase 1' region

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

Similar variants

HDAC6 p.Ala374Gly Uncertain significance ★★ ⚠ same type
HDAC6 c.1059+6G>C Likely benign ★★ same type
HDAC6 c.2187+20G>A Benign ★★ same type
HDAC6 p.Glu1017= Benign/Likely benign ★★ same type
HDAC6 p.Glu889= Benign ★★ same type
HDAC6 p.Gly1051= Benign/Likely benign ★★ same type
HDAC6 p.Gly1083Asp Likely benign ★★ same type
HDAC6 p.Gly930Arg Likely benign ★★ 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/hdac6-p-phe264 (accessed [today's date]).

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