Is HPS3 p.Val41fs (c.119dup) pathogenic?

HPS3 p.Val41fs (c.119dup) is classified Pathogenic in HPS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-10). No gnomAD frequency available for this variant.

How common is HPS3 p.Val41fs (c.119dup) in the general population?

HPS3 p.Val41fs (c.119dup) is no gnomAD frequency available for this variant (gnomAD).

HPS3 p.Val41fs

c.119dup · rs2473045218 · VCV1971545

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 1 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.6	GERP 1.8, 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.Val41fs
Coding: c.119dup
MANE Select: NM_032383
dbSNP: rs2473045218
Type: Duplication
Location: chr3:149129840 (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

Similar variants

HPS3 p.Val41Met Uncertain significance ★ same residue
HPS3 p.Val41= Likely benign ★ same residue
HPS3 p.Ala532_Leu533insPheThrPheSerValArgLeuIleCysTer Pathogenic/Likely pathogenic ★★ same type
HPS3 p.Leu333fs Pathogenic ★★ same type
HPS3 p.Ser302fs Likely pathogenic ★★ same type
HPS3 p.Ser399fs Likely pathogenic ★★ same type
HPS3 p.Thr273fs Pathogenic/Likely pathogenic ★★ same type
HPS3 p.Tyr197fs Pathogenic/Likely pathogenic ★★ 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/hps3-p-val41fs (accessed [today's date]).

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