Is BLOC1S3 p.Ala2Val (c.5C>T) pathogenic?

BLOC1S3 p.Ala2Val (c.5C>T) is classified Uncertain significance in BLOC1S3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-03). AlphaMissense: likely benign (0.2196); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BLOC1S3 p.Ala2Val (c.5C>T)?

BLOC1S3 p.Ala2Val (c.5C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BLOC1S3 p.Ala2Val (c.5C>T) in the general population?

BLOC1S3 p.Ala2Val (c.5C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BLOC1S3 p.Ala2Val (c.5C>T)?

AlphaMissense predicts likely benign (score 0.2196) — an in-silico prediction, not a clinical call.

BLOC1S3 p.Ala2Val

c.5C>T · rs2513836787 · VCV2322030

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2196 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,578,706)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2196	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -9.36	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 4.5	GERP -0.53, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 605 bp · p 0.64 · regional, not allelic
Overall
CADD	22.2	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

No allele count reported in gnomAD v4.1 (AN 1,578,706). 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: BLOC1S3
Protein: p.Ala2Val
Coding: c.5C>T
MANE Select: NM_212550
dbSNP: rs2513836787
Type: single nucleotide variant
Location: chr19:45179301 (GRCh38)
Gene constraint: LOEUF 1.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.38
Residue 2: the 'disordered' region

Full BLOC1S3 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

BLOC1S3 p.Ala2= Likely benign ★ same residue
BLOC1S3 p.Ala103Val Uncertain significance ★★ ⚠ same condition
BLOC1S3 p.Ala169Ser Uncertain significance ★★ ⚠ same condition
BLOC1S3 p.Arg106Pro Uncertain significance ★★ ⚠ same condition
BLOC1S3 p.Arg112Gln Uncertain significance ★★ ⚠ same condition
BLOC1S3 p.Arg112Leu Uncertain significance ★★ ⚠ same condition
BLOC1S3 p.Asp197His Uncertain significance ★★ ⚠ same condition
BLOC1S3 p.Gln150Arg 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/bloc1s3-p-ala2val (accessed [today's date]).

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