CNTNAP1 p.Leu403=
c.1209G>T · rs1173187040 · VCV2190167
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00322%, nfe)
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>A here scores Δ0.98 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.4 | GERP -0.97, phastCons 1 |
| Overall | ||
| CADD | 10.97 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00322%
European (non-Finnish) · 38/1,180,058 alleles
Filtering AF
0.00239%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0021%
Overall
0.00248%
40/1,614,130 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00322% | 31,054 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,490 |
| African / African-American | 0.00133% | 74,956 |
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
- CNTNAP1
- Protein
- p.Leu403=
- Coding
- c.1209G>T
- MANE Select
- NM_003632
- dbSNP
- rs1173187040
- Type
- single nucleotide variant
- Location
- chr17:42687884 (GRCh38)
- Gene constraint
- LOEUF 0.578 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.51
- Residue 403
- the laminin g-like 2 domain
Similar variants
- CNTNAP1 p.Arg1121Ter Pathogenic ★★ same type
- CNTNAP1 p.Arg618Ter Pathogenic/Likely pathogenic ★★ same type
- CNTNAP1 p.Arg697Ter Pathogenic/Likely pathogenic ★★ same type
- CNTNAP1 p.Arg835Ter Pathogenic ★★ same type
- CNTNAP1 p.Arg890Ter Pathogenic ★★ same type
- CNTNAP1 p.Trp672Ter Pathogenic ★★ same type
- CNTNAP1 c.3568+10G>A Uncertain significance ★★ same type
- CNTNAP1 p.Ala1322Thr 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/cntnap1-p-leu403 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown