DIS3L2 p.Gln604Ter
c.1810C>T · rs1695684357 · VCV970918
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Perlman syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 15 of 21 |
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.28 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 3.5 | GERP 0.47, phastCons 1 |
| Overall | ||
| CADD | 39.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- DIS3L2
- Protein
- p.Gln604Ter
- Coding
- c.1810C>T
- MANE Select
- NM_152383
- dbSNP
- rs1695684357
- Type
- single nucleotide variant
- Location
- chr2:232329883 (GRCh38)
- Gene constraint
- LOEUF 0.468 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 83.26 · 4 PDB
- Residue 604
- a turn
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.Glu332Ter Likely pathogenic ★★ same condition
- DIS3L2 p.Glu366Ter Pathogenic/Likely pathogenic ★★ same condition
- DIS3L2 c.1659+6T>A Uncertain significance ★★ 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-gln604ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown