UPF1 p.Ser247=
c.741C>T · VCV4941645
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0648%, eas)
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 -7.1 | GERP -2.7 |
| Overall | ||
| CADD | 0.507 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0648%
East Asian · 29/44,738 alleles
Filtering AF
0.0463%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0401%
Overall
0.011%
177/1,610,420 alleles · ultra-rare
exomes 162/1,458,092 · genomes 15/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0648% | 1,543 |
| Middle Eastern | 0.0343% | 2,916 |
| Remaining individualsnot grpmax-eligible | 0.0305% | 3,277 |
| European (non-Finnish) | 0.0095% | 10,524 |
| African / African-American | 0.008% | 12,502 |
| South Asian | 0.00774% | 12,917 |
| Admixed American | 0.00336% | 29,764 |
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.Ser247=
- Coding
- c.741C>T
- MANE Select
- NM_002911
- Type
- single nucleotide variant
- Location
- chr19:18850799 (GRCh38)
- Gene constraint
- LOEUF 0.125 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.58 · 12 PDB
- Residue 247
- the upf1 ch-rich domain; an α-helix; the 'sufficient for interaction with rent2' region
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-ser247 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown