CRELD2 p.Cys294=
c.882C>T · rs149127584 · VCV777313
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.03%, 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 -1.9 | GERP -0.091 |
| Overall | ||
| CADD | 2.953 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.03%
European (non-Finnish) · 12,149/1,175,728 alleles
Filtering AF
1.02%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.01%
Overall
0.828%
13,318/1,608,674 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 1.03% | 97 |
| Amishnot grpmax-eligible | 0.768% | 130 |
| Remaining individualsnot grpmax-eligible | 0.751% | 133 |
| Admixed American | 0.61% | 164 |
| Finnishnot grpmax-eligible | 0.207% | 483 |
| African / African-American | 0.151% | 663 |
| South Asian | 0.0871% | 1,149 |
| Middle Eastern | 0.0662% | 1,512 |
| East Asian | 0.00223% | 44,796 |
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
- CRELD2
- Protein
- p.Cys294=
- Coding
- c.882C>T
- MANE Select
- NM_024324
- dbSNP
- rs149127584
- Type
- single nucleotide variant
- Location
- chr22:49925430 (GRCh38)
- Gene constraint
- LOEUF 1.119 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.63
- Residue 294
- a disulfide bond; the egf-like 2; calcium-binding domain
Similar variants
- CRELD2 p.Ala236= Benign ★★ same type
- CRELD2 p.Gly162= Benign ★★ same type
- CRELD2 c.593-181G>T Uncertain significance ★ same type
- CRELD2 c.593-202A>T Uncertain significance ★ same type
- CRELD2 c.593-208G>T Uncertain significance ★ same type
- CRELD2 c.593-222C>T Uncertain significance ★ same type
- CRELD2 c.593-228G>A Uncertain significance ★ same type
- CRELD2 c.593-229C>T 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/creld2-p-cys294 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown