Is BLOC1S3 p.Ala90= (c.270G>A) pathogenic?

BLOC1S3 p.Ala90= (c.270G>A) is classified Benign/Likely benign in BLOC1S3 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 20.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Hermansky-Pudlak syndrome 8.

What condition is associated with BLOC1S3 p.Ala90= (c.270G>A)?

BLOC1S3 p.Ala90= (c.270G>A) is associated with Hermansky-Pudlak syndrome 8 (ClinVar).

How is Hermansky-Pudlak syndrome inherited?

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

BLOC1S3 p.Ala90=

Q: How common is BLOC1S3 p.Ala90= (c.270G>A) in the general population?

BLOC1S3 p.Ala90= (c.270G>A) is common (popmax 20.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.270G>A · rs758506 · VCV162790

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 20.9%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Hermansky-Pudlak syndrome 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5	GERP -2.9
Overall
CADD	9.368	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 20.9% African / African-American · 14,599/69,912 alleles

Filtering AF 20.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 20.5%

Overall 11.7% 177,670/1,515,430 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	20.9%	5
East Asian	19.4%	5
Middle Eastern	19.2%	5
South Asian	13.3%	7
Ashkenazi Jewishnot grpmax-eligible	13.1%	8
Remaining individualsnot grpmax-eligible	12.6%	8
European (non-Finnish)	11.1%	9
Admixed American	7.07%	14
Finnishnot grpmax-eligible	6.78%	15
Amishnot grpmax-eligible	5.4%	19

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: BLOC1S3
Protein: p.Ala90=
Coding: c.270G>A
MANE Select: NM_212550
dbSNP: rs758506
Type: single nucleotide variant
Location: chr19:45179566 (GRCh38)
Gene constraint: LOEUF 1.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.38

Full BLOC1S3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Hermansky-Pudlak syndrome 8 — 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

BLOC1S3 p.Ala169Ser Uncertain significance ★★ ⚠ same condition
BLOC1S3 p.Arg112Leu Uncertain significance ★★ ⚠ same condition
BLOC1S3 p.Gln150Arg Uncertain significance ★★ ⚠ same condition
BLOC1S3 p.Arg29Leu Conflicting classifications of pathogenicity ★ ⚠ same condition
BLOC1S3 p.Ser44Ter Pathogenic same condition
BLOC1S3 p.Ser30fs Uncertain significance ★ same condition
BLOC1S3 p.Gln150fs Pathogenic same condition
BLOC1S3 p.Leu113fs 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/bloc1s3-p-ala90 (accessed [today's date]).

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