Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 11 submitters
gnomAD v4.1
Common
common (popmax 20.5%, eas) — too common for a highly-penetrant pathogenic allele
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 3.1 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 8.006 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
20.5%
East Asian · 9,196/44,864 alleles
Filtering AF
20.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 20%
Overall
5.49%
88,567/1,613,844 alleles · common
exomes 79,103/1,461,620 · genomes 9,464/152,224 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 20.5% | 5 |
| Admixed American | 9.98% | 10 |
| Finnishnot grpmax-eligible | 9.61% | 10 |
| South Asian | 8.18% | 12 |
| Ashkenazi Jewishnot grpmax-eligible | 7.58% | 13 |
| Remaining individualsnot grpmax-eligible | 6.33% | 16 |
| African / African-American | 4.96% | 20 |
| European (non-Finnish) | 4.21% | 24 |
| Middle Eastern | 3.27% | 31 |
| Amishnot grpmax-eligible | 0.329% | 304 |
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.Cys2234=
- Coding
- c.6702T>C
- MANE Select
- NM_005045
- dbSNP
- rs2075043
- Type
- single nucleotide variant
- Location
- chr7:103540425 (GRCh38)
- Gene constraint
- LOEUF 0.276 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Residue 2234
- a disulfide bond
Similar variants
- RELN p.Cys2234Tyr Uncertain significance ★ 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-cys2234 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown