Is HPS3 p.Phe608fs (c.1824_1825del) pathogenic?

HPS3 p.Phe608fs (c.18241825del) is classified Likely pathogenic in HPS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-12). No gnomAD frequency available for this variant; Associated with Hermansky-Pudlak syndrome 3.

What condition is associated with HPS3 p.Phe608fs (c.1824_1825del)?

HPS3 p.Phe608fs (c.1824_1825del) is associated with Hermansky-Pudlak syndrome 3 (ClinVar).

How common is HPS3 p.Phe608fs (c.1824_1825del) in the general population?

HPS3 p.Phe608fs (c.1824_1825del) is no gnomAD frequency available for this variant (gnomAD).

HPS3 p.Phe608fs

c.1824_1825del · rs2473110430 · VCV2676104

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Hermansky-Pudlak syndrome 3

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 10 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.73	GERP 0.12, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: HPS3
Protein: p.Phe608fs
Coding: c.1824_1825del
MANE Select: NM_032383
dbSNP: rs2473110430
Type: Deletion
Location: chr3:149158796 (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 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

HPS3 p.Ala135fs Pathogenic/Likely pathogenic ★★ same condition
HPS3 p.Arg284fs Pathogenic ★★ same condition
HPS3 p.Arg30fs Pathogenic/Likely pathogenic ★★ same condition
HPS3 p.Asn623fs Pathogenic/Likely pathogenic ★★ same condition
HPS3 p.Asn83fs Pathogenic/Likely pathogenic ★★ same condition
HPS3 p.Asn96fs Likely pathogenic ★★ same condition
HPS3 p.Cys417fs Likely pathogenic ★★ same condition
HPS3 p.Cys561fs 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-phe608fs (accessed [today's date]).

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