Is CEP89 p.Arg34Cys (c.100C>T) pathogenic?

CEP89 p.Arg34Cys (c.100C>T) is classified Uncertain significance in CEP89 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-22). AlphaMissense: ambiguous (0.4867); Very rare (popmax 0.0073%, eas).

How common is CEP89 p.Arg34Cys (c.100C>T) in the general population?

CEP89 p.Arg34Cys (c.100C>T) is very rare (popmax 0.0073%, eas) (gnomAD).

What do computational predictors say about CEP89 p.Arg34Cys (c.100C>T)?

AlphaMissense predicts ambiguous (score 0.4867) — an in-silico prediction, not a clinical call.

CEP89 p.Arg34Cys

c.100C>T · rs141650808 · VCV2409081

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4867 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0073%, eas)

Computational evidence

Protein change
AlphaMissense	0.4867	ambiguous
REVEL	0.463	indeterminate
SaProt	LLR -8.37	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 93 kb · p 0.011 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0073% East Asian · 3/41,100 alleles

Filtering AF 0.00193% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00154% 24/1,562,594 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0073%	13,700
Remaining individualsnot grpmax-eligible	0.00499%	20,027
South Asian	0.00476%	21,020
African / African-American	0.00137%	72,794
European (non-Finnish)	0.00113%	88,603

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.Arg34Cys
Coding: c.100C>T
MANE Select: NM_032816
dbSNP: rs141650808
Type: single nucleotide variant
Location: chr19:32966406 (GRCh38)
Gene constraint: LOEUF 1.173 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.08
Residue 34: the 'disordered' region

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

Similar variants

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
CEP89 p.Arg324Cys 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-arg34cys (accessed [today's date]).

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