Is HPS3 p.Arg822Ter (c.2464C>T) pathogenic?

HPS3 p.Arg822Ter (c.2464C>T) is classified Pathogenic in HPS3 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-17). Very rare (popmax 0.00223%, eas); Associated with Hermansky-Pudlak syndrome.

What condition is associated with HPS3 p.Arg822Ter (c.2464C>T)?

HPS3 p.Arg822Ter (c.2464C>T) is associated with Hermansky-Pudlak syndrome, Hermansky-Pudlak syndrome 3 (ClinVar).

How common is HPS3 p.Arg822Ter (c.2464C>T) in the general population?

HPS3 p.Arg822Ter (c.2464C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Hermansky-Pudlak syndrome inherited?

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

HPS3 p.Arg822Ter

c.2464C>T · rs369855073 · VCV930923

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Hermansky-Pudlak syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.6	GERP -3.6, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,860 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000992% 16/1,613,350 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,860
Finnishnot grpmax-eligible	0.00156%	64,010
European (non-Finnish)	0.0011%	90,725
South Asian	0.0011%	91,058

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.Arg822Ter
Coding: c.2464C>T
MANE Select: NM_000096 · reported on NM_032383
dbSNP: rs369855073
Type: single nucleotide variant
Location: chr3:149162861 (GRCh38)

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

Also linked: Hermansky-Pudlak syndrome 3

For Hermansky-Pudlak syndrome (Orphanet):

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

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-arg822ter (accessed [today's date]).

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