CPSF1 p.Pro438=
c.1314G>A · VCV3770694
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0969%, 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 -9.4 | GERP -4 |
| Overall | ||
| CADD | 0.43 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0969%
European (non-Finnish) · 1,143/1,179,994 alleles
Filtering AF
0.0922%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0903%
Overall
0.0803%
1,295/1,612,636 alleles · ultra-rare
exomes 1,183/1,460,308 · genomes 112/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0969% | 1,032 |
| Remaining individualsnot grpmax-eligible | 0.096% | 1,041 |
| Admixed American | 0.0816% | 1,225 |
| Middle Eastern | 0.0495% | 2,021 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0473% | 2,114 |
| Finnishnot grpmax-eligible | 0.0192% | 5,214 |
| African / African-American | 0.0147% | 6,822 |
| South Asian | 0.00329% | 30,359 |
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
- CPSF1
- Protein
- p.Pro438=
- Coding
- c.1314G>A
- MANE Select
- NM_013291
- Type
- single nucleotide variant
- Location
- chr8:144399354 (GRCh38)
- Gene constraint
- LOEUF 0.74 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.97 · 13 PDB
- Residue 438
- a UniProt-annotated variant site (in myp27)
Similar variants
- CPSF1 p.Ala1319Thr Uncertain significance ★★ ⚠ same type
- CPSF1 p.Thr561Ile Uncertain significance ★★ ⚠ same type
- CPSF1 p.Gly722= Likely benign ★★ same type
- CPSF1 p.Leu1360= Likely benign ★★ same type
- CPSF1 p.Pro654= Likely benign ★★ same type
- CPSF1 c.539+1G>A Likely pathogenic ★ same type
- CPSF1 c.1119+2T>G Uncertain significance ★ same type
- CPSF1 c.1119+5G>T 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/cpsf1-p-pro438 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown