NLGN3 p.Pro149=
c.447G>A · VCV4951444
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.046%, mid)
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 0.42 | GERP -4.1, phastCons 0.99 |
| Overall | ||
| CADD | 8.548 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.046%
Middle Eastern · 2/4,346 alleles
Filtering AF
0.00814%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00341%
Overall
0.0024%
29/1,208,298 alleles · ultra-rare
exomes 29/1,094,878 · genomes 0/113,420 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.046% | 2,173 |
| Admixed American | 0.00434% | 23,017 |
| East Asian | 0.00296% | 33,818 |
| European (non-Finnish) | 0.00247% | 40,566 |
| Remaining individualsnot grpmax-eligible | 0.0021% | 47,553 |
| South Asian | 0.00176% | 56,888 |
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.Pro149=
- Coding
- c.447G>A
- MANE Select
- NM_181303
- Type
- single nucleotide variant
- Location
- chrX:71148196 (GRCh38)
- Structure
- AlphaFold pLDDT 76.80 · 1 PDB
Similar variants
- NLGN3 p.Pro149Ser Uncertain significance ★ ⚠ same residue
- NLGN3 p.Arg748Gln Uncertain significance ★★ ⚠ same type
- NLGN3 p.Arg785Cys Uncertain significance ★★ ⚠ same type
- NLGN3 p.Arg785His Uncertain significance ★★ ⚠ same type
- NLGN3 p.Arg847Gln Uncertain significance ★★ ⚠ same type
- NLGN3 p.Asp492Asn Uncertain significance ★★ ⚠ same type
- NLGN3 p.Leu31Phe Uncertain significance ★★ ⚠ same type
- NLGN3 p.Leu477Phe Uncertain significance ★★ ⚠ same type
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-pro149 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown