Is HPGD p.Val32= (c.96A>G) pathogenic?

HPGD p.Val32= (c.96A>G) is classified Likely benign in HPGD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-16). Very rare (popmax 0.004%, afr).

How common is HPGD p.Val32= (c.96A>G) in the general population?

HPGD p.Val32= (c.96A>G) is very rare (popmax 0.004%, afr) (gnomAD).

HPGD p.Val32=

c.96A>G · VCV3622913

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

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 0.31	GERP -1.1, phastCons 1
Overall
CADD	15.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,938 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000867% 14/1,614,042 alleles · very rare exomes 10/1,461,834 · genomes 4/152,208 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,979
East Asian	0.00223%	44,884
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.000763%	131,111

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.Val32=
Coding: c.96A>G
MANE Select: NM_000860
Type: single nucleotide variant
Location: chr4:174522065 (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 32: a β-strand

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

Similar variants

HPGD c.218-1G>A Pathogenic ★★ same type
HPGD c.324+5G>A Pathogenic ★★ same type
HPGD c.421+1G>T Pathogenic ★★ same type
HPGD p.Ala140Pro Pathogenic ★★ same type
HPGD p.Gln68Ter Pathogenic ★★ same type
HPGD c.*157A>G Uncertain significance ★★ same type
HPGD p.Asn95Ser Uncertain significance ★★ ⚠ same type
HPGD p.Glu195Ala Uncertain significance ★★ ⚠ same type

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-val32 (accessed [today's date]).

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