Is BLTP1 c.10312+2T>C pathogenic?

BLTP1 c.10312+2T>C is classified Likely pathogenic in BLTP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-13). Very rare (popmax 0.00139%, afr); Associated with BLTP1-related disorder.

What condition is associated with BLTP1 c.10312+2T>C?

BLTP1 c.10312+2T>C is associated with BLTP1-related disorder (ClinVar).

How common is BLTP1 c.10312+2T>C in the general population?

BLTP1 c.10312+2T>C is very rare (popmax 0.00139%, afr) (gnomAD).

BLTP1 c.10312+2T>C

rs1280760946 · VCV2630724

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00139%, afr)

Conditions

BLTP1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	Δ0.98	donor loss · deltas
Pangolin	Δ0.84	loss · gain 0.23 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.8	phastCons 1
Non-coding constraint	Z 1.32	1 kb window · o/e 0.89 · regional · uncalibrated
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00139% African / African-American · 1/72,072 alleles

Filtering AF 3.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.0002% 3/1,501,234 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00139%	72,072
European (non-Finnish)	0.000184%	544,028

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: BLTP1
Coding: c.10312+2T>C
MANE Select: NM_001384125
dbSNP: rs1280760946
Type: single nucleotide variant
Location: chr4:122313689 (GRCh38)

Full BLTP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BLTP1-related disorder

Similar variants

BLTP1 p.Arg968Cys Likely pathogenic ★★ ⚠ same condition
BLTP1 p.His3063Arg Uncertain significance ★★ same condition
BLTP1 c.11513+1G>C Likely pathogenic ★ same condition
BLTP1 c.5184+1G>T Likely pathogenic ★ same condition
BLTP1 p.Arg3190Ter Likely pathogenic ★ same condition
BLTP1 p.Phe3799Ser Uncertain significance ★ same condition
BLTP1 p.Val1878Ala Uncertain significance ⚠ same condition
BLTP1 c.6378+10T>C Benign 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/bltp1-c-10312-plus-2t-c (accessed [today's date]).

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