RELN p.Cys1440=
c.4320T>C · rs1584308763 · VCV746156
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
2
Norman-Roberts syndrome
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 4 | GERP 0.75, phastCons 1 |
| Overall | ||
| CADD | 7.773 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,026 alleles
Overall
6.2e-05%
1/1,614,138 alleles · very rare
exomes 1/1,461,798 · genomes 0/152,340 · joint denominator
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
- RELN
- Protein
- p.Cys1440=
- Coding
- c.4320T>C
- MANE Select
- NM_005045
- dbSNP
- rs1584308763
- Type
- single nucleotide variant
- Location
- chr7:103574283 (GRCh38)
- Gene constraint
- LOEUF 0.276 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Residue 1440
- the egf-like 3 domain
Similar variants
- RELN c.3912+2T>G Likely pathogenic ★★ same condition
- RELN c.7349+2T>C Likely pathogenic ★★ same condition
- RELN p.Arg1622Ter Pathogenic/Likely pathogenic ★★ same condition
- RELN c.1893-3C>T Uncertain significance ★★ same condition
- RELN c.227-3C>T Uncertain significance ★★ same condition
- RELN c.2465+5G>T Uncertain significance ★★ same condition
- RELN c.6072+3A>G Uncertain significance ★★ same condition
- RELN c.6072+4C>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/reln-p-cys1440 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown