Is HPGD p.Pro144= (c.432C>T) pathogenic?

HPGD p.Pro144= (c.432C>T) is classified Benign/Likely benign in HPGD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-26). Rare (popmax 0.548%, afr); Associated with hypertrophic osteoarthropathy, primary, autosomal recessive, 1.

How common is HPGD p.Pro144= (c.432C>T) in the general population?

HPGD p.Pro144= (c.432C>T) is rare (popmax 0.548%, afr) (gnomAD).

HPGD p.Pro144=

Q: What condition is associated with HPGD p.Pro144= (c.432C>T)?

HPGD p.Pro144= (c.432C>T) is associated with hypertrophic osteoarthropathy, primary, autosomal recessive, 1, isolated congenital digital clubbing (ClinVar).

c.432C>T · rs148100548 · VCV727926

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.548%, afr)

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 -0.12	GERP -3.9, phastCons 0.003
Overall
CADD	2.658	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.548% African / African-American · 411/74,974 alleles

Filtering AF 0.504% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.487%

Overall 0.0308% 496/1,612,502 alleles · rare exomes 260/1,460,204 · genomes 236/152,298 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.548%	182
Remaining individualsnot grpmax-eligible	0.0545%	1,836
Middle Eastern	0.0495%	2,020
Admixed American	0.0367%	2,726
South Asian	0.00988%	10,117
East Asian	0.00223%	44,862
European (non-Finnish)	0.00136%	73,666

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.Pro144=
Coding: c.432C>T
MANE Select: NM_000860
dbSNP: rs148100548
Type: single nucleotide variant
Location: chr4:174495614 (GRCh38)
Gene constraint: LOEUF 1.28 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.82 · 6 PDB

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-pro144 (accessed [today's date]).

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