Is HGD c.652del pathogenic?

HGD c.652del is classified Pathogenic in HGD (ClinVar, Single submitter, 3 submitters; last evaluated 2022-08-10). Very rare (popmax 0.00136%, nfe); Associated with alkaptonuria.

What condition is associated with HGD c.652del?

HGD c.652del is associated with alkaptonuria (ClinVar).

How common is HGD c.652del in the general population?

HGD c.652del is very rare (popmax 0.00136%, nfe) (gnomAD).

How is Alkaptonuria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

HGD c.652del

rs786204662 · VCV189061

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Conditions

alkaptonuria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.9	GERP 1.9, phastCons 1
Non-coding constraint	Z -0.30	1 kb window · o/e 1.02 · regional · uncalibrated
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% European (non-Finnish) · 16/1,180,008 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.000991% 16/1,613,926 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: HGD
Coding: c.652del
MANE Select: NM_000187
dbSNP: rs786204662
Type: Deletion
Location: chr3:120644441 (GRCh38)
Gene constraint: LOEUF 1.199 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.85 · 2 PDB

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

Disease context

alkaptonuria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Alkaptonuria (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult, Infancy
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

HGD p.Arg197fs Pathogenic ★★ same condition
HGD p.Ser59fs Pathogenic ★★ same condition
HGD c.283-5del Benign/Likely benign ★★ same condition
HGD c.413_434+35del Pathogenic ★ same condition
HGD c.434+1del Pathogenic ★ same condition
HGD p.Arg225fs Pathogenic ★ same condition
HGD p.Asn38fs Pathogenic ★ same condition
HGD p.Asp420fs Likely pathogenic ★ same condition

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/hgd-c-652del (accessed [today's date]).

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