CNTLN p.Ser668Phe
c.2003C>T · VCV4004481
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0034%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.014 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.6 | GERP -0.92, phastCons 0.001 |
| Regional constraint | o/e 1.30 | unconstrained · MANE · 368 kb · p 1.7e-33 · regional, not allelic |
| Overall | ||
| CADD | 6.859 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0034%
European (non-Finnish) · 40/1,176,396 alleles
Filtering AF
0.00256%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00226%
Overall
0.00281%
41/1,457,082 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0034% | 29,410 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,316 |
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.Ser668Phe
- Coding
- c.2003C>T
- MANE Select
- NM_017738
- Type
- single nucleotide variant
- Location
- chr9:17388177 (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-ser668phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown