Is CEP89 p.Ser504Leu (c.1511C>T) pathogenic?

CEP89 p.Ser504Leu (c.1511C>T) is classified Conflicting classifications of pathogenicity in CEP89 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-02). AlphaMissense: likely benign (0.0756); Very rare (popmax 0.0044%, sas).

How common is CEP89 p.Ser504Leu (c.1511C>T) in the general population?

CEP89 p.Ser504Leu (c.1511C>T) is very rare (popmax 0.0044%, sas) (gnomAD).

What do computational predictors say about CEP89 p.Ser504Leu (c.1511C>T)?

AlphaMissense predicts likely benign (score 0.0756) — an in-silico prediction, not a clinical call.

CEP89 p.Ser504Leu

c.1511C>T · rs764278381 · VCV2256119

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0756 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0044%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0756	likely benign
REVEL	0.247	benign-leaning
SaProt	LLR -1.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP -0.36, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 93 kb · p 0.011 · regional, not allelic
Overall
CADD	7.659	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 0.0044% South Asian · 4/90,828 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000893%

Overall 0.00124% 20/1,612,778 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0044%	22,707
Admixed American	0.00334%	29,918
East Asian	0.00223%	44,818
Remaining individualsnot grpmax-eligible	0.0016%	62,452
African / African-American	0.00134%	74,730
European (non-Finnish)	0.000932%	107,239

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.Ser504Leu
Coding: c.1511C>T
MANE Select: NM_032816
dbSNP: rs764278381
Type: single nucleotide variant
Location: chr19:32915391 (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.Ser504= Likely benign ★ 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-ser504leu (accessed [today's date]).

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