DIS3L2 p.Cys396=
c.1188C>T · rs145607185 · VCV531937
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.029%, eas)
Conditions
1
Perlman syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.45 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.38 | gain · loss 0.04 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 2.7 | GERP 0.21, phastCons 1 |
| Overall | ||
| CADD | 17.59 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.029%
East Asian · 13/44,852 alleles
Filtering AF
0.0171%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0136%
Overall
0.00093%
15/1,613,494 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.029% | 3,450 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,470 |
| South Asian | 0.0011% | 91,068 |
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
- DIS3L2
- Protein
- p.Cys396=
- Coding
- c.1188C>T
- MANE Select
- NM_152383
- dbSNP
- rs145607185
- Type
- single nucleotide variant
- Location
- chr2:232210389 (GRCh38)
- Gene constraint
- LOEUF 0.468 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 83.26 · 4 PDB
- Residue 396
- a β-strand
Similar variants
- DIS3L2 c.1740-1G>C Likely pathogenic ★★ same condition
- DIS3L2 p.Arg245Ter Pathogenic/Likely pathogenic ★★ same condition
- DIS3L2 p.Arg388Ter Pathogenic/Likely pathogenic ★★ same condition
- DIS3L2 p.Arg43Ter Pathogenic/Likely pathogenic ★★ same condition
- DIS3L2 p.Arg724Ter Pathogenic/Likely pathogenic ★★ same condition
- DIS3L2 p.Gln604Ter Pathogenic ★★ same condition
- DIS3L2 p.Glu332Ter Likely pathogenic ★★ same condition
- DIS3L2 p.Glu366Ter Pathogenic/Likely pathogenic ★★ 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/dis3l2-p-cys396 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown