Is BLOC1S5 p.Pro92Ser (c.274C>T) pathogenic?

BLOC1S5 p.Pro92Ser (c.274C>T) is classified Uncertain significance in BLOC1S5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-14). AlphaMissense: likely benign (0.3059); Ultra-rare (popmax 0.0254%, afr); Associated with Inborn genetic diseases.

What condition is associated with BLOC1S5 p.Pro92Ser (c.274C>T)?

BLOC1S5 p.Pro92Ser (c.274C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BLOC1S5 p.Pro92Ser (c.274C>T) in the general population?

BLOC1S5 p.Pro92Ser (c.274C>T) is ultra-rare (popmax 0.0254%, afr) (gnomAD).

What do computational predictors say about BLOC1S5 p.Pro92Ser (c.274C>T)?

AlphaMissense predicts likely benign (score 0.3059) — an in-silico prediction, not a clinical call.

BLOC1S5 p.Pro92Ser

c.274C>T · VCV3480940

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3059 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0254%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3059	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -9.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 0.027, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 49 kb · p 0.53 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0254% African / African-American · 19/74,818 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.00124% 20/1,612,390 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0254%	3,938
European (non-Finnish)	8.48e-05%	1,179,308

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: BLOC1S5
Protein: p.Pro92Ser
Coding: c.274C>T
MANE Select: NM_201280
Type: single nucleotide variant
Location: chr6:8041190 (GRCh38)
Gene constraint: LOEUF 1.625 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.86

Full BLOC1S5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BLOC1S5 p.Ala15Ser Uncertain significance ★ ⚠ same condition
BLOC1S5 p.Ala182Val Uncertain significance ★ ⚠ same condition
BLOC1S5 p.Arg122Thr Uncertain significance ★ ⚠ same condition
BLOC1S5 p.Arg156Ser Uncertain significance ★ ⚠ same condition
BLOC1S5 p.Arg50Lys Uncertain significance ★ ⚠ same condition
BLOC1S5 p.Arg58His Uncertain significance ★ ⚠ same condition
BLOC1S5 p.Arg68Cys Uncertain significance ★ ⚠ same condition
BLOC1S5 p.Arg95Gly 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/bloc1s5-p-pro92ser (accessed [today's date]).

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