CLTC p.Ala247=
c.741A>G · rs2509365310 · VCV2031787
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000254%, nfe)
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 0.14 | GERP -3.8, phastCons 0.13 |
| Overall | ||
| CADD | 8.202 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000254%
European (non-Finnish) · 3/1,179,980 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000205%
3/1,461,782 alleles · very rare
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
- CLTC
- Protein
- p.Ala247=
- Coding
- c.741A>G
- MANE Select
- NM_004859
- dbSNP
- rs2509365310
- Type
- single nucleotide variant
- Location
- chr17:59651262 (GRCh38)
- Gene constraint
- LOEUF 0.104 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.62 · 10 PDB
- Residue 247
- a β-strand; the 'wd40-like repeat 5' region; the 'globular terminal domain' region
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-p-ala247 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown