Is HDAC10 p.Pro97Ser (c.289C>T) pathogenic?

HDAC10 p.Pro97Ser (c.289C>T) is classified Uncertain significance in HDAC10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.182); Ultra-rare (popmax 0.0164%, mid).

How common is HDAC10 p.Pro97Ser (c.289C>T) in the general population?

HDAC10 p.Pro97Ser (c.289C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about HDAC10 p.Pro97Ser (c.289C>T)?

AlphaMissense predicts likely benign (score 0.182) — an in-silico prediction, not a clinical call.

HDAC10 p.Pro97Ser

c.289C>T · rs1210536214 · VCV2465841

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.182 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.182	likely benign
REVEL	0.518	indeterminate
SaProt	LLR -9.42	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; 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	28.8	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00062% 10/1,612,650 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
African / African-American	0.00133%	74,930
European (non-Finnish)	0.000678%	147,473

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.Pro97Ser
Coding: c.289C>T
MANE Select: NM_032019
dbSNP: rs1210536214
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.Pro97Ala Uncertain significance ★ ⚠ same residue
HDAC10 p.Pro97Leu 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-pro97ser (accessed [today's date]).

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