CLCC1 p.Pro496=
c.1488T>C · rs201091112 · VCV1617256
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0346%, 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 -6 | GERP -3.4 |
| Overall | ||
| CADD | 1.963 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0346%
African / African-American · 26/75,062 alleles
Filtering AF
0.0242%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0208%
Overall
0.00173%
28/1,614,234 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0346% | 2,887 |
| Admixed American | 0.00167% | 60,030 |
| European (non-Finnish) | 8.47e-05% | 1,180,050 |
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
- CLCC1
- Protein
- p.Pro496=
- Coding
- c.1488T>C
- MANE Select
- NM_001377458
- dbSNP
- rs201091112
- Type
- single nucleotide variant
- Location
- chr1:108934838 (GRCh38)
- Gene constraint
- LOEUF 0.778 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.13
- Residue 496
- the 'disordered' region; a UniProt-annotated variant site (found in a patient with sporadic als)
Similar variants
- CLCC1 p.Pro496Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
- CLCC1 p.Asp25Glu Pathogenic/Likely pathogenic ★★ same type
- CLCC1 p.Ala245Thr Uncertain significance ★★ ⚠ same type
- CLCC1 p.Ala522Thr Uncertain significance ★★ ⚠ same type
- CLCC1 p.Arg208His Uncertain significance ★★ ⚠ same type
- CLCC1 p.Arg377Trp Uncertain significance ★★ ⚠ same type
- CLCC1 p.Arg381Trp Uncertain significance ★★ ⚠ same type
- CLCC1 p.Arg401Gly 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/clcc1-p-pro496 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown