Is HPS1 p.Phe30= (c.90C>T) pathogenic?

HPS1 p.Phe30= (c.90C>T) is classified Conflicting classifications of pathogenicity in HPS1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-13). Rare (popmax 0.114%, eas); Associated with Hermansky-Pudlak syndrome 1.

What condition is associated with HPS1 p.Phe30= (c.90C>T)?

HPS1 p.Phe30= (c.90C>T) is associated with Hermansky-Pudlak syndrome 1, Hermansky-Pudlak syndrome (ClinVar).

How common is HPS1 p.Phe30= (c.90C>T) in the general population?

HPS1 p.Phe30= (c.90C>T) is rare (popmax 0.114%, eas) (gnomAD).

HPS1 p.Phe30=

c.90C>T · rs765362355 · VCV794999

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.114%, eas)

Conditions

Hermansky-Pudlak syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.81	GERP -2.9
Overall
CADD	2.432	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.114% East Asian · 51/44,872 alleles

Filtering AF 0.0888% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0799%

Overall 0.00496% 80/1,613,528 alleles · rare exomes 68/1,461,546 · genomes 12/151,982 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.114%	880
African / African-American	0.00401%	24,943
South Asian	0.00329%	30,357
European (non-Finnish)	0.00178%	56,177
Admixed American	0.00167%	59,980
Remaining individualsnot grpmax-eligible	0.0016%	62,460

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: HPS1
Protein: p.Phe30=
Coding: c.90C>T
MANE Select: NM_000195
dbSNP: rs765362355
Type: single nucleotide variant
Location: chr10:98443151 (GRCh38)
Gene constraint: LOEUF 0.879 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.44 · 1 PDB

Full HPS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Hermansky-Pudlak syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Hermansky-Pudlak syndrome

Similar variants

PYROXD2 p.Gly30Cys Uncertain significance ★ ⚠ same residue
HPS1 c.1335+1G>A Likely pathogenic ★★ same condition
HPS1 c.1744-2A>C Pathogenic/Likely pathogenic ★★ same condition
HPS1 c.1857+1G>A Likely pathogenic ★★ same condition
HPS1 c.1857+2T>C Pathogenic/Likely pathogenic ★★ same condition
HPS1 c.1858-1G>A Pathogenic/Likely pathogenic ★★ same condition
HPS1 c.1940+1G>A Pathogenic/Likely pathogenic ★★ same condition
HPS1 c.1940+2T>C 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/hps1-p-phe30 (accessed [today's date]).

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