DIS3L2 p.Leu399=
c.1197C>T · rs758998342 · VCV1087050
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
1
Perlman syndrome
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 -6.9 | GERP -4.2 |
| Overall | ||
| CADD | 4.019 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,994 alleles
Filtering AF
0.000292%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000211%
Overall
0.000616%
9/1,460,940 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,994 |
| European (non-Finnish) | 0.000678% | 147,417 |
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.Leu399=
- Coding
- c.1197C>T
- MANE Select
- NM_152383
- dbSNP
- rs758998342
- Type
- single nucleotide variant
- Location
- chr2:232210398 (GRCh38)
- Gene constraint
- LOEUF 0.468 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 83.26 · 4 PDB
Similar variants
- DIS3L2 p.Leu399Phe Uncertain significance ★ ⚠ same residue
- DIS3L2 p.Leu399Val Uncertain significance ★ ⚠ same residue
- 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
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-leu399 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown