DIS3L2 p.Ser765=
c.2295T>C · rs763103187 · VCV241973
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.2%, afr)
Conditions
1
Perlman syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.122 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -5.2 | GERP -1.2 |
| Overall | ||
| CADD | 2.407 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.2%
African / African-American · 851/71,212 alleles
Filtering AF
1.13%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1%
Overall
0.0843%
1,330/1,577,830 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.2% | 84 |
| Middle Eastern | 0.204% | 489 |
| Admixed American | 0.154% | 650 |
| East Asian | 0.132% | 755 |
| Remaining individualsnot grpmax-eligible | 0.126% | 792 |
| South Asian | 0.0504% | 1,985 |
| Finnishnot grpmax-eligible | 0.0242% | 4,132 |
| European (non-Finnish) | 0.0158% | 6,345 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0138% | 7,220 |
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.Ser765=
- Coding
- c.2295T>C
- MANE Select
- NM_152383
- dbSNP
- rs763103187
- Type
- single nucleotide variant
- Location
- chr2:232334636 (GRCh38)
- Gene constraint
- LOEUF 0.468 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 83.26 · 4 PDB
- Residue 765
- an α-helix
Similar variants
- DIS3L2 p.Ser765Asn 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
- DIS3L2 p.Glu332Ter 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-ser765 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown