Is CPSF1 p.Leu384Val (c.1150C>G) pathogenic?

CPSF1 p.Leu384Val (c.1150C>G) is classified Uncertain significance in CPSF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-22). AlphaMissense: likely pathogenic (0.8818); Absent from gnomAD v4.1.

How common is CPSF1 p.Leu384Val (c.1150C>G) in the general population?

CPSF1 p.Leu384Val (c.1150C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPSF1 p.Leu384Val (c.1150C>G)?

AlphaMissense predicts likely pathogenic (score 0.8818) — an in-silico prediction, not a clinical call.

CPSF1 p.Leu384Val

c.1150C>G · rs1554865676 · VCV2284646

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8818 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8818	likely pathogenic
REVEL	0.128	moderately benign-leaning
SaProt	LLR -7.78	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP -0.46, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 708 bp · p 0.56 · regional, not allelic
Overall
CADD	23.6	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.Leu384Val
Coding: c.1150C>G
MANE Select: NM_013291
dbSNP: rs1554865676
Type: single nucleotide variant
Location: chr8:144399680 (GRCh38)
Gene constraint: LOEUF 0.74 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.97 · 13 PDB
Residue 384: a UniProt-annotated variant site (in myp27); a β-strand

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

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-leu384val (accessed [today's date]).

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