CIROP p.Ser427=
c.1281C>T · rs143902594 · VCV2644088
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.382%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.20 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.3 | GERP -4.1 |
| Overall | ||
| CADD | 0.429 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.382%
African / African-American · 219/57,324 alleles
Filtering AF
0.341%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.325%
Overall
0.0384%
270/702,984 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.382% | 262 |
| Middle Eastern | 0.16% | 624 |
| Remaining individualsnot grpmax-eligible | 0.052% | 1,925 |
| Admixed American | 0.028% | 3,572 |
| South Asian | 0.00296% | 33,790 |
| East Asian | 0.00268% | 37,284 |
| European (non-Finnish) | 0.0026% | 38,499 |
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
- CIROP
- Protein
- p.Ser427=
- Coding
- c.1281C>T
- MANE Select
- NM_001354640
- dbSNP
- rs143902594
- Type
- single nucleotide variant
- Location
- chr14:23102120 (GRCh38)
- Structure
- AlphaFold pLDDT 73.73
- Residue 427
- a UniProt-annotated variant site (in htx12)
Similar variants
- CIROP c.988+1G>C Pathogenic ★ same type
- CIROP p.Gln528Ter Likely pathogenic ★ same type
- CIROP p.Glu376Lys Likely pathogenic ★ same type
- CIROP c.2159+2T>A Uncertain significance ★ same type
- CIROP p.Arg22Ter Conflicting classifications of pathogenicity ★ same type
- CIROP p.Gly180Arg Uncertain significance ★ ⚠ same type
- CIROP p.Gly511Glu Uncertain significance ★ ⚠ same type
- CIROP p.Ser31Phe Conflicting classifications of pathogenicity ★ ⚠ 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/cirop-p-ser427 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown