Is HGD p.Arg96= (c.288A>G) pathogenic?

HGD p.Arg96= (c.288A>G) is classified Likely benign in HGD (ClinVar, Single submitter, 1 submitter; last evaluated 2019-02-08). Very rare (popmax 0.00134%, afr); Associated with alkaptonuria.

What condition is associated with HGD p.Arg96= (c.288A>G)?

HGD p.Arg96= (c.288A>G) is associated with alkaptonuria (ClinVar).

How common is HGD p.Arg96= (c.288A>G) in the general population?

HGD p.Arg96= (c.288A>G) is very rare (popmax 0.00134%, afr) (gnomAD).

How is Alkaptonuria inherited?

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

HGD p.Arg96=

c.288A>G · rs776344570 · VCV1080293

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

alkaptonuria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.45	GERP -2.1, phastCons 1
Overall
CADD	9.024	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,812 alleles

Overall 0.000124% 2/1,611,678 alleles · very rare exomes 1/1,459,602 · genomes 1/152,076 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,812
European (non-Finnish)	8.49e-05%	1,178,182

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
Protein: p.Arg96=
Coding: c.288A>G
MANE Select: NM_000187
dbSNP: rs776344570
Type: single nucleotide variant
Location: chr3:120652646 (GRCh38)
Gene constraint: LOEUF 1.199 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.85 · 2 PDB
Residue 96: a β-strand

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

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HGD c.16-1G>A Pathogenic ★★ same condition
HGD c.342+1G>A Pathogenic/Likely pathogenic ★★ same condition
HGD c.342+1G>T Pathogenic ★★ same condition
HGD c.342+3A>C Pathogenic/Likely pathogenic ★★ same condition
HGD c.469+1G>C 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-p-arg96 (accessed [today's date]).

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