Is HDAC7 p.Pro807Thr (c.2419C>A) pathogenic?

HDAC7 p.Pro807Thr (c.2419C>A) is classified Uncertain significance in HDAC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: ambiguous (0.4036); Very rare (popmax 0.00893%, eas).

How common is HDAC7 p.Pro807Thr (c.2419C>A) in the general population?

HDAC7 p.Pro807Thr (c.2419C>A) is very rare (popmax 0.00893%, eas) (gnomAD).

What do computational predictors say about HDAC7 p.Pro807Thr (c.2419C>A)?

AlphaMissense predicts ambiguous (score 0.4036) — an in-silico prediction, not a clinical call.

HDAC7 p.Pro807Thr

c.2419C>A · VCV4675201

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4036 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00893%, eas)

Computational evidence

Protein change
AlphaMissense	0.4036	ambiguous
REVEL	0.418	indeterminate
SaProt	LLR -12.02	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 5,459 bp · p 6.7e-12 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P768T vs ClinVar P807T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00893% East Asian · 4/44,772 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000372% 6/1,612,262 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00893%	11,193
European (non-Finnish)	0.00017%	589,720

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: HDAC7
Protein: p.Pro807Thr
Coding: c.2419C>A
MANE Select: NM_015401
Type: single nucleotide variant
Location: chr12:47787746 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.90 · 6 PDB
Residue 807: the 'histone deacetylase' region

Full HDAC7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

HDAC7 p.Pro807Ala Uncertain significance ★ ⚠ same residue
HDAC7 p.Pro807Arg Uncertain significance ★ ⚠ same residue
HDAC7 p.Pro807His Uncertain significance ★ ⚠ same residue
HDAC7 p.Pro807Ser Uncertain significance ★ ⚠ same residue
HDAC7 p.Arg201= Benign/Likely benign ★★ same type
HDAC7 p.Leu233= Benign/Likely benign ★★ same type
HDAC7 p.Thr243= Benign ★★ same type
HDAC7 p.Ala138Val 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/hdac7-p-pro807thr (accessed [today's date]).

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