Is DLG3 p.Ile145= (c.435C>T) pathogenic?

DLG3 p.Ile145= (c.435C>T) is classified Benign/Likely benign in DLG3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-25). Very rare (popmax 0.00655%, amr).

How common is DLG3 p.Ile145= (c.435C>T) in the general population?

DLG3 p.Ile145= (c.435C>T) is very rare (popmax 0.00655%, amr) (gnomAD).

DLG3 p.Ile145=

c.435C>T · rs145494926 · VCV2660824

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00655%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -3.7
Overall
CADD	7.849	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00655% Admixed American · 3/45,780 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00128%

Overall 0.0114% 138/1,209,656 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.44%	227
Remaining individualsnot grpmax-eligible	0.0357%	2,801
Admixed Americangrpmax	0.00655%	15,260
European (non-Finnish)	0.00235%	42,622

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DLG3
Protein: p.Ile145=
Coding: c.435C>T
MANE Select: NM_021120
dbSNP: rs145494926
Type: single nucleotide variant
Location: chrX:70449385 (GRCh38)
Structure: AlphaFold pLDDT 74.35 · 3 PDB
Residue 145: the pdz 1 domain; a β-strand

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-ile145 (accessed [today's date]).

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