Is CPSF3 p.Ser482= (c.1446A>G) pathogenic?

CPSF3 p.Ser482= (c.1446A>G) is classified Likely benign in CPSF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-01). Very rare (popmax 0.00475%, nfe).

How common is CPSF3 p.Ser482= (c.1446A>G) in the general population?

CPSF3 p.Ser482= (c.1446A>G) is very rare (popmax 0.00475%, nfe) (gnomAD).

CPSF3 p.Ser482=

c.1446A>G · VCV3777887

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00475%, 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 -0.23	GERP -4, phastCons 0.004
Overall
CADD	7.333	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00475% European (non-Finnish) · 56/1,179,532 alleles

Filtering AF 0.00375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00337%

Overall 0.00354% 57/1,612,172 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00475%	21,063
Remaining individualsnot grpmax-eligible	0.0016%	62,406

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: CPSF3
Protein: p.Ser482=
Coding: c.1446A>G
MANE Select: NM_016207
Type: single nucleotide variant
Location: chr2:9452963 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.41 · 10 PDB
Residue 482: a β-strand

Full CPSF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPSF3 p.Ile354Met Uncertain significance ★★ ⚠ same type
CPSF3 c.51-2165C>G Uncertain significance ★ same type
CPSF3 p.Ala147Val Uncertain significance ★ ⚠ same type
CPSF3 p.Ala190Val Uncertain significance ★ ⚠ same type
CPSF3 p.Ala430Thr Uncertain significance ★ ⚠ same type
CPSF3 p.Ala516Val Uncertain significance ★ ⚠ same type
CPSF3 p.Ala6Ser Uncertain significance ★ ⚠ same type
CPSF3 p.Arg215His 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/cpsf3-p-ser482 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown