DIS3L2 p.Pro612=
c.1836G>C · rs202227137 · VCV241965
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000679%, nfe)
Conditions
1
Perlman syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.035 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -8.2 | GERP -3.1 |
| Overall | ||
| CADD | 0.121 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000679%
European (non-Finnish) · 8/1,177,458 alleles
Filtering AF
0.000292%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000211%
Overall
0.000498%
8/1,607,572 alleles · very rare
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.Pro612=
- Coding
- c.1836G>C
- MANE Select
- NM_152383
- dbSNP
- rs202227137
- Type
- single nucleotide variant
- Location
- chr2:232329909 (GRCh38)
- Gene constraint
- LOEUF 0.468 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 83.26 · 4 PDB
- Residue 612
- an α-helix
Similar variants
- DIS3L2 p.Pro612Leu Uncertain significance ★★ ⚠ same residue
- DIS3L2 p.Pro612Ser Uncertain significance ★★ ⚠ same residue
- DIS3L2 p.Pro612Arg Uncertain significance ★ ⚠ same residue
- DIS3L2 p.Pro612Gln 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
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-pro612 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown