Is HPS3 p.His288= (c.864C>T) pathogenic?

HPS3 p.His288= (c.864C>T) is classified Likely benign in HPS3 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-03-27). Very rare (popmax 0.00271%, afr); Associated with Hermansky-Pudlak syndrome.

What condition is associated with HPS3 p.His288= (c.864C>T)?

HPS3 p.His288= (c.864C>T) is associated with Hermansky-Pudlak syndrome (ClinVar).

How common is HPS3 p.His288= (c.864C>T) in the general population?

HPS3 p.His288= (c.864C>T) is very rare (popmax 0.00271%, afr) (gnomAD).

How is Hermansky-Pudlak syndrome inherited?

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

HPS3 p.His288=

c.864C>T · rs146928432 · VCV991438

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00271%, afr)

Conditions

Hermansky-Pudlak syndrome

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 -11	GERP -4
Overall
CADD	0.011	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00271% African / African-American · 2/73,810 alleles

Filtering AF 0.00045% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000168%

Overall 0.000186% 3/1,609,732 alleles · very rare exomes 1/1,460,838 · genomes 2/148,894 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00271%	36,905
Remaining individualsnot grpmax-eligible	0.0016%	62,402

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: HPS3
Protein: p.His288=
Coding: c.864C>T
MANE Select: NM_032383
dbSNP: rs146928432
Type: single nucleotide variant
Location: chr3:149141168 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.67

Full HPS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Hermansky-Pudlak syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hermansky-Pudlak syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

HPS3 c.1163+1G>A Pathogenic ★★ same condition
HPS3 c.1691+1G>A Pathogenic ★★ same condition
HPS3 p.Arg397Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
HPS3 p.Arg530Ter Pathogenic/Likely pathogenic ★★ same condition
HPS3 p.Gln245Ter Pathogenic/Likely pathogenic ★★ same condition
HPS3 p.Gln368Ter Likely pathogenic ★★ same condition
HPS3 p.Glu275Ter Likely pathogenic ★★ same condition
HPS3 p.Glu621Ter Pathogenic/Likely 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/hps3-p-his288 (accessed [today's date]).

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