Is BLOC1S6 p.Asp83= (c.249C>T) pathogenic?

BLOC1S6 p.Asp83= (c.249C>T) is classified Likely benign in BLOC1S6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-09). Very rare (popmax 0.0011%, sas); Associated with Hermansky-Pudlak syndrome 9.

What condition is associated with BLOC1S6 p.Asp83= (c.249C>T)?

BLOC1S6 p.Asp83= (c.249C>T) is associated with Hermansky-Pudlak syndrome 9 (ClinVar).

How common is BLOC1S6 p.Asp83= (c.249C>T) in the general population?

BLOC1S6 p.Asp83= (c.249C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Familial hemophagocytic lymphohistiocytosis inherited?

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

BLOC1S6 p.Asp83=

c.249C>T · rs771647965 · VCV2815237

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Hermansky-Pudlak syndrome 9

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 -0.68	GERP -4.1, phastCons 0.015
Overall
CADD	6.982	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,966 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000274% 4/1,458,996 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,966
European (non-Finnish)	0.000255%	392,633

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: BLOC1S6
Protein: p.Asp83=
Coding: c.249C>T
MANE Select: NM_012388
dbSNP: rs771647965
Type: single nucleotide variant
Location: chr15:45603124 (GRCh38)
Gene constraint: LOEUF 1.5 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.10
Residue 83: a UniProt-annotated variant site (in hps9; reduces nk cell cytolytic activity; increases lamp1/cd107a and cd63 levels at the cell membrane)

Full BLOC1S6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Hermansky-Pudlak syndrome 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial hemophagocytic lymphohistiocytosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Infancy
Prevalence: 1-9 / 100 000 (Sweden)

Similar variants

BLOC1S6 p.Gln78Ter Pathogenic ★★ same condition
BLOC1S6 p.Ser67Ter Pathogenic/Likely pathogenic ★★ same condition
BLOC1S6 p.Arg154Gln Uncertain significance ★★ ⚠ same condition
BLOC1S6 p.Arg154Ter Uncertain significance ★★ same condition
BLOC1S6 p.Arg15Trp Uncertain significance ★★ ⚠ same condition
BLOC1S6 p.Arg167Ser Uncertain significance ★★ ⚠ same condition
BLOC1S6 p.Asp35Asn Uncertain significance ★★ ⚠ same condition
BLOC1S6 p.Gln141Ter Uncertain significance ★★ 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/bloc1s6-p-asp83 (accessed [today's date]).

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