Is CEP89 p.Cys628fs (c.1882dup) pathogenic?

CEP89 p.Cys628fs (c.1882dup) is classified Uncertain significance in CEP89 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-15). Very rare (popmax 0.000597%, nfe).

How common is CEP89 p.Cys628fs (c.1882dup) in the general population?

CEP89 p.Cys628fs (c.1882dup) is very rare (popmax 0.000597%, nfe) (gnomAD).

CEP89 p.Cys628fs

c.1882dup · rs1198152978 · VCV2963290

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000597%, nfe)

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 17 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.68	GERP -1.6, phastCons 1
Overall
CADD	33.0	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 0.000597% European (non-Finnish) · 7/1,173,056 alleles

Filtering AF 0.000248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00016%

Overall 0.000498% 8/1,605,676 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00161%	62,234
European (non-Finnish)grpmax	0.000597%	167,579

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CEP89
Protein: p.Cys628fs
Coding: c.1882dup
MANE Select: NM_032816
dbSNP: rs1198152978
Type: Duplication
Location: chr19:32887834 (GRCh38)
Gene constraint: LOEUF 1.173 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.08

Full CEP89 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP89 c.39+177dup Benign ★ same type
CEP89 c.595+14dup Likely benign ★ 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/cep89-p-cys628fs (accessed [today's date]).

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