CLCC1 p.Lys514=
c.1542G>A · rs150029224 · VCV1093722
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0875%, 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 2 | GERP 0.84, phastCons 0.94 |
| Overall | ||
| CADD | 6.108 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0875%
European (non-Finnish) · 1,033/1,180,036 alleles
Filtering AF
0.0831%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0813%
Overall
0.0698%
1,127/1,614,050 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0875% | 1,142 |
| Remaining individualsnot grpmax-eligible | 0.064% | 1,562 |
| Finnishnot grpmax-eligible | 0.0359% | 2,784 |
| Admixed American | 0.025% | 4,000 |
| African / African-American | 0.0214% | 4,683 |
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.Lys514=
- Coding
- c.1542G>A
- MANE Select
- NM_001377458
- dbSNP
- rs150029224
- Type
- single nucleotide variant
- Location
- chr1:108934784 (GRCh38)
- Gene constraint
- LOEUF 0.778 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.13
- Residue 514
- the 'disordered' region; a UniProt-annotated variant site (found in a patient with sporadic als)
Similar variants
- CLCC1 p.Lys514Thr Uncertain significance ★★ ⚠ 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-lys514 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown