Is HGD p.Val284= (c.852T>C) pathogenic?

HGD p.Val284= (c.852T>C) is classified Likely benign in HGD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-24). Very rare (popmax 6.84e-05%); Associated with alkaptonuria.

What condition is associated with HGD p.Val284= (c.852T>C)?

HGD p.Val284= (c.852T>C) is associated with alkaptonuria (ClinVar).

How common is HGD p.Val284= (c.852T>C) in the general population?

HGD p.Val284= (c.852T>C) is very rare (popmax 6.84e-05%) (gnomAD).

How is Alkaptonuria inherited?

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

HGD p.Val284=

c.852T>C · rs1352452997 · VCV2983546

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Conditions

alkaptonuria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.159	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.48 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.5	GERP -1.3, phastCons 1
Overall
CADD	7.456	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,502 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
Protein: p.Val284=
Coding: c.852T>C
MANE Select: NM_000187
dbSNP: rs1352452997
Type: single nucleotide variant
Location: chr3:120641616 (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 c.1007-2A>T Pathogenic ★★ same condition
HGD c.1188+1G>A Pathogenic ★★ same condition
HGD c.15+1G>A Pathogenic/Likely pathogenic ★★ same condition
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-val284 (accessed [today's date]).

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