CADPS2 p.Ser994=
c.2982G>A · rs376397626 · VCV3067489
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. | ||
| REVEL | 0.237 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.2 | GERP -5.6, phastCons 0.001 |
| Overall | ||
| CADD | 7.805 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0223%
East Asian · 10/44,872 alleles
Filtering AF
0.012%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00917%
Overall
0.0049%
79/1,613,666 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0223% | 4,487 |
| African / African-American | 0.00934% | 10,710 |
| European (non-Finnish) | 0.00517% | 19,340 |
| Admixed American | 0.00167% | 60,004 |
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
- CADPS2
- Protein
- p.Ser994=
- Coding
- c.2982G>A
- MANE Select
- NM_017954
- dbSNP
- rs376397626
- Type
- single nucleotide variant
- Location
- chr7:122393222 (GRCh38)
- Gene constraint
- LOEUF 0.699 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.91
- Residue 994
- the mhd1 domain; the 'interaction with drd2' region
Similar variants
- CADPS2 p.Ser994Leu Uncertain significance ★ ⚠ same residue
- CADPS2 c.3718-15A>C Benign ★★ same type
- CADPS2 p.Ala298Thr Benign ★★ same type
- CADPS2 p.Asp1088Asn Likely benign ★★ same type
- CADPS2 p.Glu1010Lys Benign ★★ same type
- CADPS2 p.Leu154= Likely benign ★★ same type
- CADPS2 p.Lys338= Benign ★★ same type
- CADPS2 p.Met828Val Benign ★★ ⚠ 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/cadps2-p-ser994 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown