Is NLGN3 p.Pro201= (c.603C>G) pathogenic?

NLGN3 p.Pro201= (c.603C>G) is classified Conflicting classifications of pathogenicity in NLGN3 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-06-05). Rare (popmax 0.241%, afr); Associated with Inborn genetic diseases.

What condition is associated with NLGN3 p.Pro201= (c.603C>G)?

NLGN3 p.Pro201= (c.603C>G) is associated with Inborn genetic diseases (ClinVar).

How common is NLGN3 p.Pro201= (c.603C>G) in the general population?

NLGN3 p.Pro201= (c.603C>G) is rare (popmax 0.241%, afr) (gnomAD).

NLGN3 p.Pro201=

c.603C>G · rs35794236 · VCV290693

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.241%, afr)

Conditions

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 -3.6	GERP -4.1
Overall
CADD	4.732	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.241% African / African-American · 138/57,378 alleles

Filtering AF 0.208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.195%

Overall 0.0122% 148/1,210,465 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.241%	416
Remaining individualsnot grpmax-eligible	0.0168%	5,954
South Asian	0.00176%	56,842
European (non-Finnish)	0.000112%	895,175

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.Pro201=
Coding: c.603C>G
MANE Select: NM_181303
dbSNP: rs35794236
Type: single nucleotide variant
Location: chrX:71155239 (GRCh38)
Structure: AlphaFold pLDDT 76.80 · 1 PDB

Full NLGN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NLGN3 p.Pro201Thr Uncertain significance ★ ⚠ same residue
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

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-pro201 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown