DIS3L2 p.Phe782=
c.2346C>T · rs375456340 · VCV706205
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0151%, amr)
Conditions
1
Perlman syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.254 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -8 | GERP -1.8 |
| Overall | ||
| CADD | 8.964 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0151%
Admixed American · 9/59,796 alleles
Filtering AF
0.00776%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0058%
Overall
0.000931%
15/1,610,702 alleles · ultra-rare
exomes 14/1,458,474 · genomes 1/152,228 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0151% | 6,644 |
| East Asian | 0.00224% | 44,704 |
| South Asian | 0.0011% | 90,580 |
| European (non-Finnish) | 0.000339% | 294,706 |
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.Phe782=
- Coding
- c.2346C>T
- MANE Select
- NM_152383
- dbSNP
- rs375456340
- Type
- single nucleotide variant
- Location
- chr2:232334687 (GRCh38)
- Gene constraint
- LOEUF 0.468 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 83.26 · 4 PDB
- Residue 782
- a β-strand
Similar variants
- DIS3L2 p.Phe782Leu Uncertain significance ★ ⚠ same residue
- DIS3L2 p.Phe782Val 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-phe782 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown