CNTLN p.Ser307Pro
c.919T>C · rs202140760 · VCV2409510
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0544%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.111 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.27 | acceptor loss, 9 bp away · masked 0 · deltas |
| Constraint at this position | ||
| Conservation | phyloP 2.8 | GERP 1.8, phastCons 1 |
| Regional constraint | o/e 1.30 | unconstrained · MANE · 368 kb · p 1.7e-33 · regional, not allelic |
| Overall | ||
| CADD | 22.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0544%
South Asian · 46/84,590 alleles
Filtering AF
0.0419%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0374%
Overall
0.0321%
506/1,575,110 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0544% | 1,839 |
| European (non-Finnish) | 0.0369% | 2,711 |
| Remaining individualsnot grpmax-eligible | 0.0361% | 2,770 |
| African / African-American | 0.00822% | 12,163 |
| Admixed American | 0.0039% | 25,637 |
| East Asian | 0.00233% | 42,928 |
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
- CNTLN
- Protein
- p.Ser307Pro
- Coding
- c.919T>C
- MANE Select
- NM_017738
- dbSNP
- rs202140760
- Type
- single nucleotide variant
- Location
- chr9:17273802 (GRCh38)
- Gene constraint
- LOEUF 1.431 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.14
Similar variants
- CNTLN p.Phe935Leu Uncertain significance ★★ same type
- CNTLN c.3115-9A>T Benign ★★ same type
- CNTLN p.Ala1256= Benign ★★ same type
- CNTLN p.Asp553Glu Benign ★★ same type
- CNTLN p.Gln800= Benign ★★ same type
- CNTLN p.Ser404Asn Benign ★★ same type
- CNTLN p.Ala1005Val Uncertain significance ★ same type
- CNTLN p.Ala1248Thr 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/cntln-p-ser307pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown