CPSF1 p.Ala232Asp
c.695C>A · VCV3496603
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9979 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
AlphaMissense, SaProt · REVEL no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9979 | likely pathogenic · top 7% in CPSF1 |
|---|---|---|
| REVEL | 0.439 | indeterminate |
| SaProt | LLR -9.05 | tolerated |
| ⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.20 | constrained · MANE · 249 bp · p 1.8e-06 · regional, not allelic |
| Overall | ||
| CADD | 23.7 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CPSF1
- Protein
- p.Ala232Asp
- Coding
- c.695C>A
- MANE Select
- NM_013291
- Type
- single nucleotide variant
- Location
- chr8:144400485 (GRCh38)
- Gene constraint
- LOEUF 0.74 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.97 · 13 PDB
- Residue 232
- a UniProt-annotated variant site (in myp27); a turn
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.Pro438= 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
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-ala232asp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown