Is NLGN3 p.Pro103Thr (c.307C>A) pathogenic?

NLGN3 p.Pro103Thr (c.307C>A) is classified Uncertain significance in NLGN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-20). AlphaMissense: likely benign (0.1664); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with NLGN3 p.Pro103Thr (c.307C>A)?

NLGN3 p.Pro103Thr (c.307C>A) is associated with Inborn genetic diseases (ClinVar).

How common is NLGN3 p.Pro103Thr (c.307C>A) in the general population?

NLGN3 p.Pro103Thr (c.307C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NLGN3 p.Pro103Thr (c.307C>A)?

AlphaMissense predicts likely benign (score 0.1664) — an in-silico prediction, not a clinical call.

NLGN3 p.Pro103Thr

c.307C>A · rs1288368410 · VCV3200429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1664 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1664	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -9.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.20 · evaluated, not missing
Pangolin	Δ0.21	gain · loss 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 2.2	GERP -2.7, phastCons 0.99
Regional constraint	o/e 0.63	unconstrained · MANE · 7,479 bp · p 1e-06 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NLGN3
Protein: p.Pro103Thr
Coding: c.307C>A
MANE Select: NM_181303
dbSNP: rs1288368410
Type: single nucleotide variant
Location: chrX:71148056 (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.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-pro103thr (accessed [today's date]).

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