DLG4 p.Cys445=
c.1335C>T · rs369619048 · VCV2647318
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.85%, sas)
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 0.017 | GERP -4.8, phastCons 0.3 |
| Overall | ||
| CADD | 12.02 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.85%
South Asian · 766/90,080 alleles
Filtering AF
0.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.78%
Overall
0.065%
1,046/1,609,876 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.85% | 118 |
| Middle Eastern | 0.248% | 404 |
| Ashkenazi Jewishnot grpmax-eligible | 0.187% | 535 |
| Remaining individualsnot grpmax-eligible | 0.077% | 1,299 |
| Admixed American | 0.0353% | 2,832 |
| African / African-American | 0.024% | 4,165 |
| European (non-Finnish) | 0.0103% | 9,737 |
| East Asian | 0.00224% | 44,732 |
| Finnishnot grpmax-eligible | 0.00157% | 63,704 |
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
- DLG4
- Protein
- p.Cys445=
- Coding
- c.1335C>T
- MANE Select
- NM_001321075
- dbSNP
- rs369619048
- Type
- single nucleotide variant
- Location
- chr17:7194462 (GRCh38)
- Gene constraint
- LOEUF 0.151 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.00 · 24 PDB
- Residue 445
- a UniProt-annotated variant site (in mrd62); the sh3 domain
Similar variants
- DLG4 c.1084-1G>T Pathogenic/Likely pathogenic ★★ same type
- DLG4 c.1478+2T>C Pathogenic/Likely pathogenic ★★ same type
- DLG4 c.1543+2T>C Pathogenic/Likely pathogenic ★★ same type
- DLG4 c.1592-1G>A Pathogenic/Likely pathogenic ★★ same type
- DLG4 c.1693+1G>A Pathogenic/Likely pathogenic ★★ same type
- DLG4 c.1866+2T>C Pathogenic/Likely pathogenic ★★ same type
- DLG4 c.210+1G>T Likely pathogenic ★★ same type
- DLG4 c.211-2A>G Pathogenic/Likely pathogenic ★★ 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/dlg4-p-cys445 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown