Is HDAC7 p.His771Arg (c.2312A>G) pathogenic?

HDAC7 p.His771Arg (c.2312A>G) is classified Uncertain significance in HDAC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-26). AlphaMissense: likely pathogenic (0.5709); Absent from gnomAD v4.1.

How common is HDAC7 p.His771Arg (c.2312A>G) in the general population?

HDAC7 p.His771Arg (c.2312A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HDAC7 p.His771Arg (c.2312A>G)?

AlphaMissense predicts likely pathogenic (score 0.5709) — an in-silico prediction, not a clinical call.

HDAC7 p.His771Arg

c.2312A>G · VCV3524470

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5709 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5709	likely pathogenic
REVEL	0.696	pathogenic-leaning
SaProt	LLR -11.22	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	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	24.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM H732R vs ClinVar H771R) — verify the residue.

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: HDAC7
Protein: p.His771Arg
Coding: c.2312A>G
MANE Select: NM_015401
Type: single nucleotide variant
Location: chr12:47788088 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.90 · 6 PDB
Residue 771: the 'histone deacetylase' region; an α-helix

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

Similar variants

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
HDAC7 p.Ala266Val Uncertain significance ★ ⚠ same type
HDAC7 p.Ala337Gly Uncertain significance ★ ⚠ same type
HDAC7 p.Ala337Thr Uncertain significance ★ ⚠ same type
HDAC7 p.Ala431Gly 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-his771arg (accessed [today's date]).

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