Is HDAC10 p.Phe205Ser (c.614T>C) pathogenic?

HDAC10 p.Phe205Ser (c.614T>C) is classified Uncertain significance in HDAC10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-21). AlphaMissense: likely benign (0.1862); Very rare (popmax 0.00017%, nfe).

How common is HDAC10 p.Phe205Ser (c.614T>C) in the general population?

HDAC10 p.Phe205Ser (c.614T>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about HDAC10 p.Phe205Ser (c.614T>C)?

AlphaMissense predicts likely benign (score 0.1862) — an in-silico prediction, not a clinical call.

HDAC10 p.Phe205Ser

c.614T>C · rs763403823 · VCV2620019

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1862 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1862	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -7.01	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 -0.23	GERP -2.6
Regional constraint	o/e 1.07	unconstrained · MANE · 5,522 bp · p 0.051 · regional, not allelic
Overall
CADD	8.793	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 0.00017% European (non-Finnish) · 2/1,179,944 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,460,454 alleles · very rare

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.Phe205Ser
Coding: c.614T>C
MANE Select: NM_032019
dbSNP: rs763403823
Type: single nucleotide variant
Location: chr22:50249404 (GRCh38)
Gene constraint: LOEUF 1.303 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.57
Residue 205: the 'histone deacetylase' region

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

Similar variants

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
HDAC10 p.Ala489Asp Uncertain significance ★ ⚠ same type
HDAC10 p.Ala503Thr 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-phe205ser (accessed [today's date]).

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