RELN p.Ser630=
c.1890T>C · rs1584377776 · VCV669184
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00502%, 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 -0.8 | GERP -3.2 |
| Overall | ||
| CADD | 6.567 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00502%
Admixed American · 3/59,766 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000669%
Overall
0.000372%
6/1,611,144 alleles · very rare
exomes 5/1,459,152 · genomes 1/151,992 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00502% | 19,922 |
| South Asian | 0.0011% | 91,058 |
| European (non-Finnish) | 0.00017% | 588,991 |
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.Ser630=
- Coding
- c.1890T>C
- MANE Select
- NM_005045
- dbSNP
- rs1584377776
- Type
- single nucleotide variant
- Location
- chr7:103651663 (GRCh38)
- Gene constraint
- LOEUF 0.276 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Similar variants
- RELN p.Ser630Arg Benign ★★ ⚠ same residue
- 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
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-ser630 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown