C2CD6 p.Phe528Leu
c.1582T>C · VCV3483593
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00484%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.04 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.8 | GERP -0.47, phastCons 0.97 |
| Regional constraint | o/e 0.80 | unconstrained · MANE · 49 kb · p 7.7e-16 · regional, not allelic |
| Overall | ||
| CADD | 15.73 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00484%
Admixed American · 2/41,340 alleles
Filtering AF
0.000802%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0003%
Overall
0.000374%
5/1,337,208 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00484% | 20,670 |
| European (non-Finnish) | 0.000266% | 375,413 |
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
- C2CD6
- Protein
- p.Phe528Leu
- Coding
- c.1582T>C
- MANE Select
- NM_001168221
- Type
- single nucleotide variant
- Location
- chr2:201494759 (GRCh38)
- Gene constraint
- LOEUF 0.908 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 39.82
Similar variants
- C2CD6 p.Ala1682Thr Uncertain significance ★ same type
- C2CD6 p.Ala427Gly Uncertain significance ★ ⚠ same type
- C2CD6 p.Ala54Pro Uncertain significance ★ ⚠ same type
- C2CD6 p.Ala54Ser Uncertain significance ★ ⚠ same type
- C2CD6 p.Ala646Ser Uncertain significance ★ same type
- C2CD6 p.Ala827Asp Uncertain significance ★ same type
- C2CD6 p.Arg1134Cys Uncertain significance ★ same type
- C2CD6 p.Arg1134His 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/c2cd6-p-phe528leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown