Is NRXN1 p.Ser671= (c.2013C>T) pathogenic?

NRXN1 p.Ser671= (c.2013C>T) is classified Uncertain significance in NRXN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Absent from gnomAD v4.1; Associated with Pitt-Hopkins-like syndrome 2.

What condition is associated with NRXN1 p.Ser671= (c.2013C>T)?

NRXN1 p.Ser671= (c.2013C>T) is associated with Pitt-Hopkins-like syndrome 2 (ClinVar).

How common is NRXN1 p.Ser671= (c.2013C>T) in the general population?

NRXN1 p.Ser671= (c.2013C>T) is absent from gnomAD v4.1 (gnomAD).

NRXN1 p.Ser671=

c.2013C>T · rs1359837458 · VCV899159

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Pitt-Hopkins-like syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.2	GERP -1.3, phastCons 1
Overall
CADD	8.355	PHRED · no single calibrated threshold — expert panels disagree

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: NRXN1
Protein: p.Ser671=
Coding: c.2013C>T
MANE Select: NM_001330078
dbSNP: rs1359837458
Type: single nucleotide variant
Location: chr2:50538383 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.53 · 3 PDB
Residue 671: the laminin g-like 3 domain

Full NRXN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Pitt-Hopkins-like syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NRXN1 c.832+1G>A Likely pathogenic ★★ same condition
NRXN1 p.Arg1144Ter Pathogenic/Likely pathogenic ★★ same condition
NRXN1 p.Arg1253Ter Pathogenic/Likely pathogenic ★★ same condition
NRXN1 p.Arg1260Ter Pathogenic ★★ same condition
NRXN1 p.Arg747Ter Likely pathogenic ★★ same condition
NRXN1 p.Arg855Ter Pathogenic/Likely pathogenic ★★ same condition
NRXN1 c.1320+3A>G Uncertain significance ★★ same condition
NRXN1 c.2347+4A>G 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/nrxn1-p-ser671 (accessed [today's date]).

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