CLTCL1 p.Ala352=
c.1056C>T · rs34889146 · VCV788041
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.765%, 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 -0.078 | GERP -3.8 |
| Overall | ||
| CADD | 2.484 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.765%
African / African-American · 574/75,022 alleles
Filtering AF
0.713%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.693%
Overall
0.0406%
655/1,613,966 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.765% | 131 |
| Middle Eastern | 0.0825% | 1,212 |
| Admixed American | 0.0467% | 2,143 |
| Remaining individualsnot grpmax-eligible | 0.0432% | 2,314 |
| South Asian | 0.00329% | 30,361 |
| Finnishnot grpmax-eligible | 0.00156% | 64,006 |
| European (non-Finnish) | 0.00144% | 69,404 |
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
- CLTCL1
- Protein
- p.Ala352=
- Coding
- c.1056C>T
- MANE Select
- NM_007098
- dbSNP
- rs34889146
- Type
- single nucleotide variant
- Location
- chr22:19234620 (GRCh38)
- Gene constraint
- LOEUF 0.993 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.53
- Residue 352
- the 'globular terminal domain' region
Similar variants
- CLTCL1 p.Arg1226Cys Uncertain significance ★★ ⚠ same type
- CLTCL1 p.Gln1113Lys Uncertain significance ★★ ⚠ same type
- CLTCL1 p.Gln1142Arg Uncertain significance ★★ ⚠ same type
- CLTCL1 p.Glu1212Lys Uncertain significance ★★ ⚠ same type
- CLTCL1 p.Gly464Arg Uncertain significance ★★ ⚠ same type
- CLTCL1 p.Ser1061Gly Uncertain significance ★★ ⚠ same type
- CLTCL1 p.Ser707Gly Uncertain significance ★★ ⚠ same type
- CLTCL1 p.Val948Gly 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/cltcl1-p-ala352 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown