Is HDAC7 p.Pro807Arg (c.2420C>G) pathogenic?

HDAC7 p.Pro807Arg (c.2420C>G) is classified Uncertain significance in HDAC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-30). AlphaMissense: ambiguous (0.4706); Very rare (popmax 0.0089%, nfe).

How common is HDAC7 p.Pro807Arg (c.2420C>G) in the general population?

HDAC7 p.Pro807Arg (c.2420C>G) is very rare (popmax 0.0089%, nfe) (gnomAD).

What do computational predictors say about HDAC7 p.Pro807Arg (c.2420C>G)?

AlphaMissense predicts ambiguous (score 0.4706) — an in-silico prediction, not a clinical call.

HDAC7 p.Pro807Arg

c.2420C>G · rs148606386 · VCV2355330

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4706 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0089%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4706	ambiguous
REVEL	0.45	indeterminate
SaProt	LLR -10.99	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	27.0	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 P768R vs ClinVar P807R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0089% European (non-Finnish) · 105/1,179,412 alleles

Filtering AF 0.00749% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00691%

Overall 0.00664% 107/1,612,142 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0089%	11,232
Remaining individualsnot grpmax-eligible	0.0016%	62,416
African / African-American	0.00134%	74,822

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.Pro807Arg
Coding: c.2420C>G
MANE Select: NM_015401
dbSNP: rs148606386
Type: single nucleotide variant
Location: chr12:47787745 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.90 · 6 PDB
Residue 768 UniProt numbering: 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.Pro807His Uncertain significance ★ ⚠ same residue
HDAC7 p.Pro807Ser Uncertain significance ★ same residue
HDAC7 p.Pro807Thr 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-pro807arg (accessed [today's date]).

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