CNTNAP1 p.His445=
c.1335C>T · rs1307797493 · VCV1335273
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, 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 · C>G here scores Δ0.26 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -10 | GERP -5 |
| Overall | ||
| CADD | 0.223 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,886 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000434%
7/1,613,998 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,443 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| South Asian | 0.0011% | 91,086 |
| European (non-Finnish) | 0.000254% | 393,348 |
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.His445=
- Coding
- c.1335C>T
- MANE Select
- NM_003632
- dbSNP
- rs1307797493
- Type
- single nucleotide variant
- Location
- chr17:42688490 (GRCh38)
- Gene constraint
- LOEUF 0.578 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.51
- Residue 445
- 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-his445 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown