Is DLG3 p.Leu22Pro (c.65T>C) pathogenic?

DLG3 p.Leu22Pro (c.65T>C) is classified Uncertain significance in DLG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-24). AlphaMissense: likely pathogenic (0.8676); Absent from gnomAD v4.1.

How common is DLG3 p.Leu22Pro (c.65T>C) in the general population?

DLG3 p.Leu22Pro (c.65T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DLG3 p.Leu22Pro (c.65T>C)?

AlphaMissense predicts likely pathogenic (score 0.8676) — an in-silico prediction, not a clinical call.

DLG3 p.Leu22Pro

c.65T>C · rs2519724948 · VCV1806573

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8676 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8676	likely pathogenic
REVEL	0.349	indeterminate
SaProt	LLR -7.14	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.1, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 3,743 bp · p 0.36 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

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: DLG3
Protein: p.Leu22Pro
Coding: c.65T>C
MANE Select: NM_021120
dbSNP: rs2519724948
Type: single nucleotide variant
Location: chrX:70445266 (GRCh38)
Structure: AlphaFold pLDDT 74.35 · 3 PDB

Full DLG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLG3 p.Arg211Ter Pathogenic ★★ same type
DLG3 p.Arg217Ter Pathogenic ★★ same type
DLG3 p.Arg679Ter Pathogenic/Likely pathogenic ★★ same type
DLG3 p.Arg756Ter Pathogenic ★★ same type
DLG3 p.Ala627Ser Uncertain significance ★★ ⚠ same type
DLG3 p.Arg217Gln Uncertain significance ★★ ⚠ same type
DLG3 p.Arg271Cys Uncertain significance ★★ ⚠ same type
DLG3 p.Arg472His Uncertain significance ★★ ⚠ same type

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/dlg3-p-leu22pro (accessed [today's date]).

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