Is HDAC7 p.Pro807Ala (c.2419C>G) pathogenic?

HDAC7 p.Pro807Ala (c.2419C>G) is classified Uncertain significance in HDAC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-22). AlphaMissense: likely benign (0.1426); Very rare (popmax 0.00772%, sas).

How common is HDAC7 p.Pro807Ala (c.2419C>G) in the general population?

HDAC7 p.Pro807Ala (c.2419C>G) is very rare (popmax 0.00772%, sas) (gnomAD).

What do computational predictors say about HDAC7 p.Pro807Ala (c.2419C>G)?

AlphaMissense predicts likely benign (score 0.1426) — an in-silico prediction, not a clinical call.

HDAC7 p.Pro807Ala

c.2419C>G · rs543267989 · VCV3104637

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1426 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00772%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1426	likely benign
REVEL	0.382	indeterminate
SaProt	LLR -9.78	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 5,459 bp · p 6.7e-12 · regional, not allelic
Overall
CADD	25.5	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 P768A vs ClinVar P807A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00772% South Asian · 7/90,674 alleles

Filtering AF 0.0036% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00256%

Overall 0.0011% 16/1,460,240 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00772%	12,953
East Asian	0.00223%	44,772
Admixed American	0.00167%	59,900
Remaining individualsnot grpmax-eligible	0.0016%	62,432
European (non-Finnish)	0.000509%	196,573

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: HDAC7
Protein: p.Pro807Ala
Coding: c.2419C>G
MANE Select: NM_015401
dbSNP: rs543267989
Type: single nucleotide variant
Location: chr12:47787746 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.90 · 6 PDB
Residue 807: the 'histone deacetylase' region

Full HDAC7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

HDAC7 p.Pro807Arg Uncertain significance ★ ⚠ same residue
HDAC7 p.Pro807His Uncertain significance ★ ⚠ same residue
HDAC7 p.Pro807Ser Uncertain significance ★ ⚠ same residue
HDAC7 p.Pro807Thr Uncertain significance ★ ⚠ same residue
HDAC7 p.Arg201= Benign/Likely benign ★★ same type
HDAC7 p.Leu233= Benign/Likely benign ★★ same type
HDAC7 p.Thr243= Benign ★★ same type
HDAC7 p.Ala138Val 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/hdac7-p-pro807ala (accessed [today's date]).

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