Is CPSF1 p.Val1329Gly (c.3986T>G) pathogenic?

CPSF1 p.Val1329Gly (c.3986T>G) is classified Uncertain significance in CPSF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: likely benign (0.0737); Absent from gnomAD v4.1.

How common is CPSF1 p.Val1329Gly (c.3986T>G) in the general population?

CPSF1 p.Val1329Gly (c.3986T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPSF1 p.Val1329Gly (c.3986T>G)?

AlphaMissense predicts likely benign (score 0.0737) — an in-silico prediction, not a clinical call.

CPSF1 p.Val1329Gly

c.3986T>G · VCV4656245

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0737 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0737	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -0.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 0.99, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 1,165 bp · p 0.4 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: CPSF1
Protein: p.Val1329Gly
Coding: c.3986T>G
MANE Select: NM_013291
Type: single nucleotide variant
Location: chr8:144393912 (GRCh38)
Gene constraint: LOEUF 0.74 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.97 · 13 PDB
Residue 1329: a UniProt-annotated variant site (in myp27)

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

Similar variants

CPSF1 p.Val1329Met 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-val1329gly (accessed [today's date]).

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