Is CPSF3 p.Pro371Ser (c.1111C>T) pathogenic?

CPSF3 p.Pro371Ser (c.1111C>T) is classified Uncertain significance in CPSF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). AlphaMissense: likely pathogenic (0.9003); Absent from gnomAD v4.1.

How common is CPSF3 p.Pro371Ser (c.1111C>T) in the general population?

CPSF3 p.Pro371Ser (c.1111C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPSF3 p.Pro371Ser (c.1111C>T)?

AlphaMissense predicts likely pathogenic (score 0.9003) — an in-silico prediction, not a clinical call.

CPSF3 p.Pro371Ser

c.1111C>T · VCV3836011

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9003 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9003	likely pathogenic
REVEL	0.522	indeterminate
SaProt	LLR -14.52	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 29 kb · p 1.5e-29 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: CPSF3
Protein: p.Pro371Ser
Coding: c.1111C>T
MANE Select: NM_016207
Type: single nucleotide variant
Location: chr2:9443530 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.41 · 10 PDB

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-pro371ser (accessed [today's date]).

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