CLTCL1 p.Pro526=
c.1578G>A · rs148315445 · VCV716366
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.71%, 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 -2.8 | GERP -3.2 |
| Overall | ||
| CADD | 5.979 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.71%
African / African-American · 1,285/75,028 alleles
Filtering AF
1.63%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.6%
Overall
0.111%
1,784/1,613,934 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.71% | 58 |
| Ashkenazi Jewishnot grpmax-eligible | 0.318% | 315 |
| Middle Eastern | 0.264% | 379 |
| Admixed American | 0.22% | 455 |
| Remaining individualsnot grpmax-eligible | 0.213% | 470 |
| European (non-Finnish) | 0.00983% | 10,171 |
| South Asian | 0.00878% | 11,385 |
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.Pro526=
- Coding
- c.1578G>A
- MANE Select
- NM_007098
- dbSNP
- rs148315445
- Type
- single nucleotide variant
- Location
- chr22:19232542 (GRCh38)
- Gene constraint
- LOEUF 0.993 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.53
- Residue 526
- the 'heavy chain arm' region; the 'distal segment' region
Similar variants
- CLTCL1 p.Pro526Ala Uncertain significance ★ ⚠ same residue
- CLTCL1 p.Pro526Leu Uncertain significance ★ ⚠ same residue
- 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
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-pro526 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown