Is CEP89 p.Arg39= (c.117C>T) pathogenic?

CEP89 p.Arg39= (c.117C>T) is classified Likely benign in CEP89 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-25). Ultra-rare (popmax 0.0184%, amr).

How common is CEP89 p.Arg39= (c.117C>T) in the general population?

CEP89 p.Arg39= (c.117C>T) is ultra-rare (popmax 0.0184%, amr) (gnomAD).

CEP89 p.Arg39=

c.117C>T · rs765720971 · VCV2183303

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0184%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.53	GERP 0.27, phastCons 0.99
Overall
CADD	9.378	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0184% Admixed American · 10/54,362 alleles

Filtering AF 0.00997% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00755%

Overall 0.000642% 10/1,558,448 alleles · ultra-rare exomes 9/1,406,210 · genomes 1/152,238 · joint denominator

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.Arg39=
Coding: c.117C>T
MANE Select: NM_032816
dbSNP: rs765720971
Type: single nucleotide variant
Location: chr19:32966389 (GRCh38)
Gene constraint: LOEUF 1.173 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.08
Residue 39: the 'disordered' region

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

Similar variants

CEP89 p.Arg39Cys Uncertain significance ★ ⚠ same residue
CEP89 p.Arg39His 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

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-arg39 (accessed [today's date]).

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