Is CPSF1 p.Pro110Gln (c.329C>A) pathogenic?

CPSF1 p.Pro110Gln (c.329C>A) is classified Uncertain significance in CPSF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-03). AlphaMissense: likely pathogenic (0.7498); Very rare (popmax 0.00195%, amr).

How common is CPSF1 p.Pro110Gln (c.329C>A) in the general population?

CPSF1 p.Pro110Gln (c.329C>A) is very rare (popmax 0.00195%, amr) (gnomAD).

What do computational predictors say about CPSF1 p.Pro110Gln (c.329C>A)?

AlphaMissense predicts likely pathogenic (score 0.7498) — an in-silico prediction, not a clinical call.

CPSF1 p.Pro110Gln

c.329C>A · rs782533294 · VCV2314955

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7498 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00195%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7498	likely pathogenic
REVEL	0.285	benign-leaning
SaProt	LLR -1.87	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 761 bp · p 3.3e-05 · regional, not allelic
Overall
CADD	23.5	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

Grpmax group 0.00195% Admixed American · 1/51,392 alleles

Overall 6.43e-05% 1/1,555,358 alleles · very rare exomes 1/1,403,072 · genomes 0/152,286 · joint denominator

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.Pro110Gln
Coding: c.329C>A
MANE Select: NM_013291
dbSNP: rs782533294
Type: single nucleotide variant
Location: chr8:144401269 (GRCh38)
Gene constraint: LOEUF 0.74 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.97 · 13 PDB
Residue 110: a UniProt-annotated variant site (in myp27); a turn

Full CPSF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPSF1 p.Pro110Leu Uncertain significance ★ ⚠ same residue
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

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-pro110gln (accessed [today's date]).

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