UPF1 p.Ala620=
c.1860C>T · rs34677724 · VCV1243123
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 11.1%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -11 | GERP -2.3 |
| Overall | ||
| CADD | 0.042 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
11.1%
African / African-American · 8,290/74,886 alleles
Filtering AF
10.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 10.8%
Overall
3.91%
63,056/1,611,980 alleles · common
exomes 54,548/1,459,876 · genomes 8,508/152,104 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 11.1% | 9 |
| Finnishnot grpmax-eligible | 6.42% | 16 |
| European (non-Finnish) | 3.91% | 26 |
| Remaining individualsnot grpmax-eligible | 3.51% | 29 |
| Admixed American | 2.14% | 47 |
| Ashkenazi Jewishnot grpmax-eligible | 1.32% | 76 |
| Middle Eastern | 1.26% | 79 |
| South Asian | 0.65% | 154 |
| Amishnot grpmax-eligible | 0.329% | 304 |
| East Asian | 0.0156% | 6,410 |
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.Ala620=
- Coding
- c.1860C>T
- MANE Select
- NM_002911
- dbSNP
- rs34677724
- Type
- single nucleotide variant
- Location
- chr19:18856912 (GRCh38)
- Gene constraint
- LOEUF 0.125 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.58 · 12 PDB
- Residue 620
- an α-helix; the upf1-type sf1b helicase atp-binding domain
Similar variants
- UPF1 p.Ala620Pro Uncertain significance ★ ⚠ same residue
- 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
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-ala620 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown