DIS3 p.His691=
c.2073T>C · rs1224755214 · VCV1338014
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
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 4 | GERP -3.5, phastCons 1 |
| Overall | ||
| CADD | 7.268 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,918 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.00131%
2/152,138 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
- DIS3
- Protein
- p.His691=
- Coding
- c.2073T>C
- MANE Select
- NM_014953
- dbSNP
- rs1224755214
- Type
- single nucleotide variant
- Location
- chr13:72763505 (GRCh38)
- Gene constraint
- LOEUF 1.076 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.12 · 3 PDB
- Residue 691
- the rnb domain; a β-strand
Similar variants
- DIS3 p.Ala518Thr Uncertain significance ★★ ⚠ same type
- DIS3 p.Ala401Val Benign ★★ ⚠ same type
- DIS3 p.Ter959Gln Likely benign ★★ same type
- PIBF1 p.Ile51Val Benign/Likely benign ★★ same type
- PIBF1 p.Met73Thr Benign/Likely benign ★★ same type
- DIS3 p.Arg638Ter Likely pathogenic ★ same type
- DIS3 c.228+3G>A Uncertain significance ★ same type
- DIS3 c.2511+1G>C Uncertain significance ★ same type
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/dis3-p-his691 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown