Is HPGD p.Arg163= (c.489C>T) pathogenic?

HPGD p.Arg163= (c.489C>T) is classified Benign in HPGD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-26). Common (popmax 6.66%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hypertrophic osteoarthropathy, primary, autosomal recessive, 1.

HPGD p.Arg163=

Q: What condition is associated with HPGD p.Arg163= (c.489C>T)?

HPGD p.Arg163= (c.489C>T) is associated with hypertrophic osteoarthropathy, primary, autosomal recessive, 1, isolated congenital digital clubbing (ClinVar).

Q: How common is HPGD p.Arg163= (c.489C>T) in the general population?

HPGD p.Arg163= (c.489C>T) is common (popmax 6.66%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.489C>T · rs17060544 · VCV348202

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 6.66%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

hypertrophic osteoarthropathy, primary, autosomal recessive, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.096	GERP -3.2, phastCons 0.71
Overall
CADD	6.625	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.66% African / African-American · 4,986/74,914 alleles

Filtering AF 6.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.44%

Overall 0.351% 5,653/1,610,546 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.66%	15
Remaining individualsnot grpmax-eligible	0.455%	220
Middle Eastern	0.363%	275
Admixed American	0.347%	288
South Asian	0.022%	4,551
European (non-Finnish)	0.0113%	8,848

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: HPGD
Protein: p.Arg163=
Coding: c.489C>T
MANE Select: NM_000860
dbSNP: rs17060544
Type: single nucleotide variant
Location: chr4:174495557 (GRCh38)
Gene constraint: LOEUF 1.28 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.82 · 6 PDB
Residue 163: an α-helix

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

Disease context

hypertrophic osteoarthropathy, primary, autosomal recessive, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: isolated congenital digital clubbing

Similar variants

HPGD c.324+5G>A Pathogenic ★★ same condition
HPGD c.421+1G>T Pathogenic ★★ same condition
HPGD p.Ala140Pro Pathogenic ★★ same condition
HPGD p.Gln68Ter Pathogenic ★★ same condition
HPGD c.*157A>G Uncertain significance ★★ same condition
HPGD p.Asn95Ser Uncertain significance ★★ ⚠ same condition
HPGD p.Gly114Glu Uncertain significance ★★ ⚠ same condition
HPGD p.Leu167Phe Uncertain significance ★★ ⚠ 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/hpgd-p-arg163 (accessed [today's date]).

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