Is CPSF7 p.Arg413Leu (c.1238G>T) pathogenic?

CPSF7 p.Arg413Leu (c.1238G>T) is classified Uncertain significance in CPSF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-27). AlphaMissense: likely pathogenic (0.9108); Absent from gnomAD v4.1.

How common is CPSF7 p.Arg413Leu (c.1238G>T) in the general population?

CPSF7 p.Arg413Leu (c.1238G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPSF7 p.Arg413Leu (c.1238G>T)?

AlphaMissense predicts likely pathogenic (score 0.9108) — an in-silico prediction, not a clinical call.

CPSF7 p.Arg413Leu

c.1238G>T · VCV4006410

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9108 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9108	likely pathogenic
REVEL	0.268	benign-leaning
SaProt	LLR -9.94	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	Δ0.47	acceptor gain · deltas
Pangolin	Δ0.25	gain · loss 0.17 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 18 kb · p 2.7e-11 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R422L vs ClinVar R413L) — verify the residue.

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: CPSF7
Protein: p.Arg413Leu
Coding: c.1238G>T
MANE Select: NM_001142565
Type: single nucleotide variant
Location: chr11:61411094 (GRCh38)
Gene constraint: LOEUF 0.13 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.55 · 1 PDB
Residue 413: a modified residue (phosphoserine); the 'disordered' region

Full CPSF7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPSF7 c.-15C>T Uncertain significance ★ same type
CPSF7 c.-21C>G Uncertain significance ★ same type
CPSF7 c.-56+117C>T Uncertain significance ★ same type
CPSF7 c.-56+123C>G Uncertain significance ★ same type
CPSF7 c.-56+124C>T Uncertain significance ★ same type
CPSF7 c.-56+133G>C Uncertain significance ★ same type
CPSF7 c.-56+138G>C Uncertain significance ★ same type
CPSF7 c.-56+150C>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/cpsf7-p-arg413leu (accessed [today's date]).

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