CLTC c.519+2T>A
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
Absent
absent from gnomAD v4.1
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 in a haploinsufficient gene (ClinGen) |
|---|---|---|
| Splicing | ||
| Splice region | donor +2 | canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone |
| SpliceAI | Δ0.99 | donor loss · deltas |
| Pangolin | Δ0.87 | loss · gain 0.07 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 1.9, phastCons 1 |
| Non-coding constraint | Z 3.73 | 1 kb window · o/e 0.73 · regional · uncalibrated |
| Overall | ||
| CADD | 35.0 | 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
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CLTC
- Coding
- c.519+2T>A
- MANE Select
- NM_004859
- Type
- single nucleotide variant
- Location
- chr17:59647668 (GRCh38)
- Gene constraint
- LOEUF 0.104 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.62 · 10 PDB
Similar variants
- CLTC p.Arg1165Ter Likely pathogenic ★★ same type
- CLTC p.Arg1251Ter Pathogenic/Likely pathogenic ★★ same type
- CLTC p.Arg1311Ter Likely pathogenic ★★ same type
- CLTC p.Arg63Ter Pathogenic ★★ same type
- CLTC p.Pro890Leu Pathogenic/Likely pathogenic ★★ same type
- CLTC p.Tyr1574Ter Pathogenic/Likely pathogenic ★★ same type
- CLTC p.Tyr803Ter Pathogenic/Likely pathogenic ★★ same type
- CLTC c.4605+3T>A Uncertain significance ★★ same type
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/cltc-c-519-plus-2t-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown