CASC3 p.Pro669=
c.2007C>A · rs771979816 · VCV2647735
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.247%, mid)
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 -8.8 | GERP -3.1 |
| Overall | ||
| CADD | 0.791 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.247%
Middle Eastern · 15/6,066 alleles
Filtering AF
0.152%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.123%
Overall
0.0018%
29/1,613,076 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.247% | 404 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,813 |
| Admixed American | 0.00167% | 59,806 |
| European (non-Finnish) | 0.000848% | 117,971 |
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
- CASC3
- Protein
- p.Pro669=
- Coding
- c.2007C>A
- MANE Select
- NM_007359
- dbSNP
- rs771979816
- Type
- single nucleotide variant
- Location
- chr17:40169365 (GRCh38)
- Gene constraint
- LOEUF 0.466 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 54.18 · 13 PDB
- Residue 669
- the 'necessary for localization in cytoplasmic stress granules' region; the 'disordered' region
Similar variants
- CASC3 p.Ala247Val Uncertain significance ★ ⚠ same type
- CASC3 p.Ala380Gly Uncertain significance ★ ⚠ same type
- CASC3 p.Ala472Val Uncertain significance ★ ⚠ same type
- CASC3 p.Ala618Val Uncertain significance ★ ⚠ same type
- CASC3 p.Ala641Thr Uncertain significance ★ ⚠ same type
- CASC3 p.Ala670Thr Uncertain significance ★ ⚠ same type
- CASC3 p.Ala72Ser Uncertain significance ★ ⚠ same type
- CASC3 p.Arg207His 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/casc3-p-pro669 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown