Is NLGN1 p.Pro577Arg (c.1730C>G) pathogenic?

NLGN1 p.Pro577Arg (c.1730C>G) is classified Uncertain significance in NLGN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). Very rare (popmax 0.00168%, amr); Associated with Inborn genetic diseases.

What condition is associated with NLGN1 p.Pro577Arg (c.1730C>G)?

NLGN1 p.Pro577Arg (c.1730C>G) is associated with Inborn genetic diseases (ClinVar).

How common is NLGN1 p.Pro577Arg (c.1730C>G) in the general population?

NLGN1 p.Pro577Arg (c.1730C>G) is very rare (popmax 0.00168%, amr) (gnomAD).

NLGN1 p.Pro577Arg

c.1730C>G · VCV4626189

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.414	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00168% Admixed American · 1/59,554 alleles

Overall 0.000137% 2/1,458,214 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00168%	59,554
Remaining individualsnot grpmax-eligible	0.00161%	62,260

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: NLGN1
Protein: p.Pro577Arg
Coding: c.1730C>G
MANE Select: NM_001365925
Type: single nucleotide variant
Location: chr3:174280501 (GRCh38)
Gene constraint: LOEUF 0.291 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 77.23 · 2 PDB
Residue 577: a UniProt-annotated variant site (in auts20; uncertain significance); an α-helix

Full NLGN1 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

NLGN1 p.Gln675Arg Uncertain significance ★★ same condition
NLGN1 p.Gly810Arg Uncertain significance ★★ same condition
NLGN1 p.Val325Ile Uncertain significance ★★ same condition
NLGN1 p.Ala18Glu Uncertain significance ★ same condition
NLGN1 p.Ala244Thr Uncertain significance ★ same condition
NLGN1 p.Ala27Thr Uncertain significance ★ same condition
NLGN1 p.Ala330Glu Uncertain significance ★ same condition
NLGN1 p.Ala375Thr 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/nlgn1-p-pro577arg (accessed [today's date]).

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