Is CPSF1 p.Val943fs (c.2823_2824del) pathogenic?

CPSF1 p.Val943fs (c.28232824del) is classified Conflicting classifications of pathogenicity in CPSF1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-03-01). Ultra-rare (popmax 0.0174%, afr); Associated with myopia 27.

What condition is associated with CPSF1 p.Val943fs (c.2823_2824del)?

CPSF1 p.Val943fs (c.2823_2824del) is associated with myopia 27 (ClinVar).

How common is CPSF1 p.Val943fs (c.2823_2824del) in the general population?

CPSF1 p.Val943fs (c.2823_2824del) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

CPSF1 p.Val943fs

c.2823_2824del · rs782640869 · VCV829516

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Conditions

myopia 27

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 25 of 38
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0174% African / African-American · 13/74,920 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.00806% 130/1,612,632 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,763
Middle Eastern	0.0164%	6,082
East Asian	0.00891%	11,220
South Asian	0.00879%	11,379
Finnishnot grpmax-eligible	0.0079%	12,662
European (non-Finnish)	0.00788%	12,683
Admixed American	0.00667%	14,989
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,588
Remaining individualsnot grpmax-eligible	0.0016%	62,450

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: CPSF1
Protein: p.Val943fs
Coding: c.2823_2824del
MANE Select: NM_013291
dbSNP: rs782640869
Type: Deletion
Location: chr8:144396600 (GRCh38)
Gene constraint: LOEUF 0.74 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.97 · 13 PDB
Residue 943: a UniProt-annotated variant site (in myp27); a β-strand

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

Disease context

myopia 27 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CPSF1 p.Asp719fs Likely pathogenic ★ same condition
CPSF1 p.Lys420fs Likely pathogenic ★ same condition
CPSF1 c.1882_1895-76del Uncertain significance ★ same condition
CPSF1 p.Thr561Ile Uncertain significance ★★ ⚠ same condition
CPSF1 c.539+1G>A Likely pathogenic ★ same condition
CPSF1 c.1119+5G>T Uncertain significance ★ same condition
CPSF1 c.1120-5C>T Uncertain significance ★ same condition
CPSF1 c.1752+4A>T Uncertain significance ★ same condition

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-val943fs (accessed [today's date]).

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