CLCC1 p.Phe174=
c.522C>T · rs138361021 · VCV1105413
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0223%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4.8 | GERP -0.82, phastCons 1 |
| Overall | ||
| CADD | 12.46 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0223%
East Asian · 10/44,874 alleles
Filtering AF
0.012%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00917%
Overall
0.00539%
87/1,613,740 alleles · ultra-rare
exomes 78/1,461,566 · genomes 9/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0223% | 4,487 |
| European (non-Finnish) | 0.0061% | 16,386 |
| Admixed American | 0.005% | 19,999 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,490 |
| African / African-American | 0.00133% | 74,986 |
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.Phe174=
- Coding
- c.522C>T
- MANE Select
- NM_001377458
- dbSNP
- rs138361021
- Type
- single nucleotide variant
- Location
- chr1:108943875 (GRCh38)
- Gene constraint
- LOEUF 0.778 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.13
Similar variants
- 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
- CLCC1 p.Arg443Trp 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-phe174 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown