UPF1 p.Cys545=
c.1635C>T · rs150324027 · VCV790755
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.988%, nfe)
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 -20 | GERP -2.5 |
| Overall | ||
| CADD | 2.228 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.988%
European (non-Finnish) · 11,664/1,180,030 alleles
Filtering AF
0.973%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.967%
Overall
0.798%
12,884/1,614,010 alleles · rare
exomes 12,069/1,461,624 · genomes 815/152,386 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.988% | 101 |
| Remaining individualsnot grpmax-eligible | 0.682% | 147 |
| Amishnot grpmax-eligible | 0.548% | 182 |
| Admixed American | 0.47% | 213 |
| Ashkenazi Jewishnot grpmax-eligible | 0.402% | 249 |
| Finnishnot grpmax-eligible | 0.392% | 255 |
| African / African-American | 0.163% | 615 |
| Middle Eastern | 0.033% | 3,031 |
| South Asian | 0.0154% | 6,506 |
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
- UPF1
- Protein
- p.Cys545=
- Coding
- c.1635C>T
- MANE Select
- NM_002911
- dbSNP
- rs150324027
- Type
- single nucleotide variant
- Location
- chr19:18856015 (GRCh38)
- Gene constraint
- LOEUF 0.125 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.58 · 12 PDB
- Residue 545
- an α-helix; the upf1-type sf1b helicase atp-binding domain
Similar variants
- UPF1 c.1266-32T>G Benign ★★ same type
- UPF1 c.1544+108G>A Benign ★★ same type
- UPF1 c.2300+75T>C Benign ★★ same type
- UPF1 c.232-90G>A Benign ★★ same type
- UPF1 c.2457+89G>A Benign ★★ same type
- UPF1 c.2458-85G>T Benign ★★ same type
- UPF1 c.2601-188G>C Benign ★★ same type
- UPF1 c.2601-47A>G Benign ★★ 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/upf1-p-cys545 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown