Is HPS3 p.Arg89fs (c.264_268delinsTTGTTTTTCTCCAGTT) pathogenic?

HPS3 p.Arg89fs (c.264268delinsTTGTTTTTCTCCAGTT) is classified Likely pathogenic in HPS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-17). Associated with Hermansky-Pudlak syndrome.

What condition is associated with HPS3 p.Arg89fs (c.264_268delinsTTGTTTTTCTCCAGTT)?

HPS3 p.Arg89fs (c.264_268delinsTTGTTTTTCTCCAGTT) is associated with Hermansky-Pudlak syndrome (ClinVar).

How is Hermansky-Pudlak syndrome inherited?

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

HPS3 p.Arg89fs

c.264_268delinsTTGTTTTTCTCCAGTT · VCV4816325

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Hermansky-Pudlak syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -5.2	GERP -4.2

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

Variant & gene context

Gene: HPS3
Protein: p.Arg89fs
Coding: c.264_268delinsTTGTTTTTCTCCAGTT
MANE Select: NM_032383
Type: Indel
Location: chr3:149140050 (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 p.Pro370_Ser373del Likely pathogenic ★★ same condition
HPS3 p.Arg89Cys Uncertain significance ★★ ⚠ same residue
HPS3 p.Arg89His Uncertain significance ★★ ⚠ same residue
HPS3 p.His571Ter Likely pathogenic ★ same condition
HPS3 p.Arg89Pro Uncertain significance ★ ⚠ same residue
HPS3 p.Arg89= Likely benign ★ same residue
HPS3 c.1163+1G>A Pathogenic ★★ same condition
HPS3 c.1691+1G>A 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-arg89fs (accessed [today's date]).

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