Is HDAC10 p.Pro97Ala (c.289C>G) pathogenic?

HDAC10 p.Pro97Ala (c.289C>G) is classified Uncertain significance in HDAC10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-01). AlphaMissense: likely benign (0.148); Very rare (popmax 0.000763%, nfe).

How common is HDAC10 p.Pro97Ala (c.289C>G) in the general population?

HDAC10 p.Pro97Ala (c.289C>G) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about HDAC10 p.Pro97Ala (c.289C>G)?

AlphaMissense predicts likely benign (score 0.148) — an in-silico prediction, not a clinical call.

HDAC10 p.Pro97Ala

c.289C>G · VCV4675153

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.148 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.148	likely benign
REVEL	0.521	indeterminate
SaProt	LLR -10.26	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 9.6	GERP 1.4, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 5,522 bp · p 0.051 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,179,774 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000753% 11/1,460,414 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,245
European (non-Finnish)grpmax	0.000763%	131,086

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: HDAC10
Protein: p.Pro97Ala
Coding: c.289C>G
MANE Select: NM_032019
Type: single nucleotide variant
Location: chr22:50250429 (GRCh38)
Gene constraint: LOEUF 1.303 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.57
Residue 97: the 'histone deacetylase' region

Full HDAC10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

HDAC10 p.Pro97Leu Uncertain significance ★ ⚠ same residue
HDAC10 p.Pro97Ser Uncertain significance ★ ⚠ same residue
HDAC10 p.Ala103Val Uncertain significance ★ ⚠ same type
HDAC10 p.Ala157Thr Uncertain significance ★ ⚠ same type
HDAC10 p.Ala326Val Uncertain significance ★ ⚠ same type
HDAC10 p.Ala339Val Uncertain significance ★ ⚠ same type
HDAC10 p.Ala348Val Uncertain significance ★ ⚠ same type
HDAC10 p.Ala488Thr 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/hdac10-p-pro97ala (accessed [today's date]).

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