NLGN3 p.Pro650=
c.1950G>A · rs775350500 · VCV1782065
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0141%, sas)
Conditions
1
Inborn genetic diseases
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 0.19 | GERP -1.6, phastCons 0.86 |
| Overall | ||
| CADD | 6.43 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0141%
South Asian · 8/56,805 alleles
Filtering AF
0.00694%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00506%
Overall
0.00174%
21/1,210,050 alleles · ultra-rare
exomes 19/1,098,125 · genomes 2/111,925 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0141% | 7,101 |
| East Asian | 0.00296% | 33,745 |
| Admixed American | 0.00218% | 45,840 |
| Remaining individualsnot grpmax-eligible | 0.0021% | 47,600 |
| European (non-Finnish) | 0.00112% | 89,518 |
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
- NLGN3
- Protein
- p.Pro650=
- Coding
- c.1950G>A
- MANE Select
- NM_181303
- dbSNP
- rs775350500
- Type
- single nucleotide variant
- Location
- chrX:71169500 (GRCh38)
- Structure
- AlphaFold pLDDT 76.80 · 1 PDB
- Residue 650
- the 'disordered' region
Similar variants
- NLGN3 p.Arg785Cys Uncertain significance ★★ ⚠ same condition
- NLGN3 p.Leu31Phe Uncertain significance ★★ ⚠ same condition
- NLGN3 p.Leu477Phe Uncertain significance ★★ ⚠ same condition
- NLGN3 p.Thr783Met Uncertain significance ★★ ⚠ same condition
- NLGN3 p.Val346Met Uncertain significance ★★ ⚠ same condition
- NLGN3 p.Ala750= Benign ★★ same condition
- NLGN3 p.Asn138= Likely benign ★★ same condition
- NLGN3 p.Asn138Ser Likely benign ★★ 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/nlgn3-p-pro650 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown