Is HDAC9 p.Ala635Val (c.1904C>T) pathogenic?

HDAC9 p.Ala635Val (c.1904C>T) is classified Uncertain significance in HDAC9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-06). AlphaMissense: likely benign (0.0858); Absent from gnomAD v4.1.

How common is HDAC9 p.Ala635Val (c.1904C>T) in the general population?

HDAC9 p.Ala635Val (c.1904C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HDAC9 p.Ala635Val (c.1904C>T)?

AlphaMissense predicts likely benign (score 0.0858) — an in-silico prediction, not a clinical call.

HDAC9 p.Ala635Val

c.1904C>T · VCV4034128

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0858 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,521,422)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0858	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -6.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 100 kb · p 0.013 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 A632V vs ClinVar A635V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,521,422). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: HDAC9
Protein: p.Ala635Val
Coding: c.1904C>T
MANE Select: NM_178425
Type: single nucleotide variant
Location: chr7:18727752 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.48 · 2 PDB
Residue 635: 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-ala635val (accessed [today's date]).

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