CNTNAP1 p.Ile649=
c.1947C>T · rs142269872 · VCV2186038
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.939%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2 | GERP 0.53, phastCons 1 |
| Overall | ||
| CADD | 11.18 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.939%
South Asian · 855/91,092 alleles
Filtering AF
0.886%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.866%
Overall
0.0568%
917/1,614,224 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.939% | 107 |
| Remaining individualsnot grpmax-eligible | 0.0368% | 2,718 |
| Middle Eastern | 0.033% | 3,031 |
| African / African-American | 0.00533% | 18,763 |
| East Asian | 0.00446% | 22,444 |
| European (non-Finnish) | 0.00254% | 39,334 |
| Admixed American | 0.00167% | 60,030 |
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.Ile649=
- Coding
- c.1947C>T
- MANE Select
- NM_003632
- dbSNP
- rs142269872
- Type
- single nucleotide variant
- Location
- chr17:42690830 (GRCh38)
- Gene constraint
- LOEUF 0.578 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.51
- Residue 649
- a UniProt-annotated variant site (in chn3); a UniProt-annotated variant site (in lccs7 and chn3); the fibrinogen c-terminal 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-ile649 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown