CLTC p.Ala1244=
c.3732T>C · rs753214660 · VCV1577480
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0174%, afr)
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 0.27 | GERP -1.7, phastCons 1 |
| Overall | ||
| CADD | 9.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0174%
African / African-American · 13/74,922 alleles
Filtering AF
0.0103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00813%
Overall
0.00112%
18/1,614,006 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0174% | 5,763 |
| Admixed American | 0.005% | 20,001 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| European (non-Finnish) | 8.47e-05% | 1,180,002 |
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.Ala1244=
- Coding
- c.3732T>C
- MANE Select
- NM_004859
- dbSNP
- rs753214660
- Type
- single nucleotide variant
- Location
- chr17:59682760 (GRCh38)
- Gene constraint
- LOEUF 0.104 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.62 · 10 PDB
- Residue 1244
- the 'heavy chain arm' region; the 'proximal segment' region; the 'involved in binding clathrin light chain' region; a UniProt-annotated variant site (in mrd56)
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-ala1244 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown