Is NLGN1 p.Pro103Ser (c.307C>T) pathogenic?

NLGN1 p.Pro103Ser (c.307C>T) is classified Uncertain significance in NLGN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-11). Ultra-rare (popmax 0.0143%, sas); Associated with Inborn genetic diseases.

What condition is associated with NLGN1 p.Pro103Ser (c.307C>T)?

NLGN1 p.Pro103Ser (c.307C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NLGN1 p.Pro103Ser (c.307C>T) in the general population?

NLGN1 p.Pro103Ser (c.307C>T) is ultra-rare (popmax 0.0143%, sas) (gnomAD).

NLGN1 p.Pro103Ser

c.307C>T · rs773132929 · VCV2610584

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.113	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.5, phastCons 1
Overall
CADD	15.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0143% South Asian · 13/91,084 alleles

Filtering AF 0.00844% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00661%

Overall 0.000868% 14/1,613,604 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0143%	7,006
European (non-Finnish)	8.48e-05%	1,179,760

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.Pro103Ser
Coding: c.307C>T
MANE Select: NM_001365925
dbSNP: rs773132929
Type: single nucleotide variant
Location: chr3:173604905 (GRCh38)
Gene constraint: LOEUF 0.291 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 77.23 · 2 PDB
Residue 103: 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-pro103ser (accessed [today's date]).

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