Is HDAC9 p.Ser751Cys (c.2252C>G) pathogenic?

HDAC9 p.Ser751Cys (c.2252C>G) is classified Uncertain significance in HDAC9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-02-08). AlphaMissense: likely benign (0.1137); Absent from gnomAD v4.1.

How common is HDAC9 p.Ser751Cys (c.2252C>G) in the general population?

HDAC9 p.Ser751Cys (c.2252C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HDAC9 p.Ser751Cys (c.2252C>G)?

AlphaMissense predicts likely benign (score 0.1137) — an in-silico prediction, not a clinical call.

HDAC9 p.Ser751Cys

c.2252C>G · rs2484321522 · VCV2497693

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1137 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1137	likely benign
REVEL	0.302	indeterminate
SaProt	LLR -10.33	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 247 kb · p 5.3e-07 · regional, not allelic
Overall
CADD	27.8	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 S748C vs ClinVar S751C) — 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: HDAC9
Protein: p.Ser751Cys
Coding: c.2252C>G
MANE Select: NM_178425
dbSNP: rs2484321522
Type: single nucleotide variant
Location: chr7:18793382 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.48 · 2 PDB
Residue 751: the 'histone deacetylase' region

Full HDAC9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

HDAC9 p.Pro390= Benign ★★ same type
HDAC9 c.1910-2A>G Uncertain significance ★ same type
HDAC9 p.Ala1028Val Uncertain significance ★ same type
HDAC9 p.Ala1068Val Uncertain significance ★ same type
HDAC9 p.Ala140Ser Uncertain significance ★ ⚠ same type
HDAC9 p.Ala238Thr Uncertain significance ★ ⚠ same type
HDAC9 p.Ala339Ser Uncertain significance ★ ⚠ same type
HDAC9 p.Ala346Thr 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/hdac9-p-ser751cys (accessed [today's date]).

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