Is CPSF3 p.Val601Ile (c.1801G>A) pathogenic?

CPSF3 p.Val601Ile (c.1801G>A) is classified Uncertain significance in CPSF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.0708); Very rare (popmax 0.00167%, amr).

How common is CPSF3 p.Val601Ile (c.1801G>A) in the general population?

CPSF3 p.Val601Ile (c.1801G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CPSF3 p.Val601Ile (c.1801G>A)?

AlphaMissense predicts likely benign (score 0.0708) — an in-silico prediction, not a clinical call.

CPSF3 p.Val601Ile

c.1801G>A · rs1194935212 · VCV3076891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0708 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0708	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -7.18	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 3.7	GERP 0.26, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 20 kb · p 0.011 · regional, not allelic
Overall
CADD	16.71	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

Grpmax group 0.00167% Admixed American · 1/59,960 alleles

Overall 6.85e-05% 1/1,460,300 alleles · very rare

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: CPSF3
Protein: p.Val601Ile
Coding: c.1801G>A
MANE Select: NM_016207
dbSNP: rs1194935212
Type: single nucleotide variant
Location: chr2:9467721 (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-val601ile (accessed [today's date]).

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