NRXN1 p.Tyr1237=
c.3711C>T · rs1699528369 · VCV1110188
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000339%, nfe)
Conditions
1
Pitt-Hopkins-like syndrome 2
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 1.3 | GERP -1.2, phastCons 1 |
| Overall | ||
| CADD | 5.072 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000339%
European (non-Finnish) · 4/1,180,038 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.000248%
4/1,613,958 alleles · very rare
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
- NRXN1
- Protein
- p.Tyr1237=
- Coding
- c.3711C>T
- MANE Select
- NM_001330078
- dbSNP
- rs1699528369
- Type
- single nucleotide variant
- Location
- chr2:50091330 (GRCh38)
- Gene constraint
- LOEUF 0.317 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.53 · 3 PDB
- Residue 1237
- the laminin g-like 6 domain
Similar variants
- NRXN1 c.832+1G>A Likely pathogenic ★★ same condition
- NRXN1 p.Arg1144Ter Pathogenic/Likely pathogenic ★★ same condition
- NRXN1 p.Arg1253Ter Pathogenic/Likely pathogenic ★★ same condition
- NRXN1 p.Arg1260Ter Pathogenic ★★ same condition
- NRXN1 p.Arg747Ter Likely pathogenic ★★ same condition
- NRXN1 p.Arg855Ter Pathogenic/Likely pathogenic ★★ same condition
- NRXN1 c.1320+3A>G Uncertain significance ★★ same condition
- NRXN1 c.2347+4A>G Uncertain significance ★★ same condition
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/nrxn1-p-tyr1237 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown