Is DLGAP1 p.Arg340Ter (c.1018C>T) pathogenic?

DLGAP1 p.Arg340Ter (c.1018C>T) is classified Uncertain significance in DLGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-08-05). Absent from gnomAD v4.1; Associated with DLGAP1-related synaptopathy.

What condition is associated with DLGAP1 p.Arg340Ter (c.1018C>T)?

DLGAP1 p.Arg340Ter (c.1018C>T) is associated with DLGAP1-related synaptopathy (ClinVar).

How common is DLGAP1 p.Arg340Ter (c.1018C>T) in the general population?

DLGAP1 p.Arg340Ter (c.1018C>T) is absent from gnomAD v4.1 (gnomAD).

DLGAP1 p.Arg340Ter

c.1018C>T · VCV4974492

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

DLGAP1-related synaptopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 5 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 6.1, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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: DLGAP1
Protein: p.Arg340Ter
Coding: c.1018C>T
MANE Select: NM_004746
Type: single nucleotide variant
Location: chr18:3814213 (GRCh38)
Gene constraint: LOEUF 0.224 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.85 · 3 PDB

Full DLGAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DLGAP1-related synaptopathy

Similar variants

DLGAP1 p.Trp810Ter Uncertain significance ★ same condition
DLGAP1 p.Leu269Gln Uncertain significance ⚠ same condition
DLGAP1 p.Thr69Pro Uncertain significance ⚠ same condition
DLGAP1 c.1351-3C>T Likely benign same condition
DLGAP1 c.957+4405C>G Likely benign same condition
DLGAP1 c.957+4506C>T Likely benign same condition
DLGAP1 c.957+4508T>C Benign same condition
DLGAP1 c.957+4875G>C 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/dlgap1-p-arg340ter (accessed [today's date]).

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