Is CEP89 p.Ter784Gln (c.2350T>C) pathogenic?

CEP89 p.Ter784Gln (c.2350T>C) is classified Benign in CEP89 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 36.4%, nfe) — too common for a highly-penetrant pathogenic allele.

CEP89 p.Ter784Gln

Q: How common is CEP89 p.Ter784Gln (c.2350T>C) in the general population?

CEP89 p.Ter784Gln (c.2350T>C) is common (popmax 36.4%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2350T>C · rs745961 · VCV1669354

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Common

common (popmax 36.4%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP -3, phastCons 0.99
Overall
CADD	5.302	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 36.4% European (non-Finnish) · 426,852/1,171,634 alleles

Filtering AF 36.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 36.3%

Overall 32.1% 514,331/1,602,036 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	36.4%	3
Amishnot grpmax-eligible	30.5%	3
Finnishnot grpmax-eligible	30.3%	3
Remaining individualsnot grpmax-eligible	30%	3
Ashkenazi Jewishnot grpmax-eligible	28.8%	3
Middle Eastern	24.3%	4
South Asian	20.9%	5
Admixed American	15.4%	6
African / African-American	9.76%	10
East Asian	9.4%	11

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.Ter784Gln
Coding: c.2350T>C
MANE Select: NM_032816
dbSNP: rs745961
Type: single nucleotide variant
Location: chr19:32879164 (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 p.Ter784Leu Uncertain significance ★ same residue
CEP89 p.Ala291Thr Uncertain significance ★★ ⚠ same type
CEP89 p.Ala291Val Uncertain significance ★★ ⚠ same type
CEP89 p.Ala372Thr Uncertain significance ★★ ⚠ same type
CEP89 p.Ala54Val Uncertain significance ★★ ⚠ same type
CEP89 p.Ala680Thr Uncertain significance ★★ ⚠ same type
CEP89 p.Ala780Asp Uncertain significance ★★ ⚠ same type
CEP89 p.Arg102Trp 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/cep89-p-ter784gln (accessed [today's date]).

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