Is CEP89 p.Pro357Leu (c.1070C>T) pathogenic?

CEP89 p.Pro357Leu (c.1070C>T) is classified Uncertain significance in CEP89 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-25). AlphaMissense: ambiguous (0.3741); Absent from gnomAD v4.1.

How common is CEP89 p.Pro357Leu (c.1070C>T) in the general population?

CEP89 p.Pro357Leu (c.1070C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP89 p.Pro357Leu (c.1070C>T)?

AlphaMissense predicts ambiguous (score 0.3741) — an in-silico prediction, not a clinical call.

CEP89 p.Pro357Leu

c.1070C>T · VCV3657793

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3741 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3741	ambiguous
REVEL	0.206	benign-leaning
SaProt	LLR -6.83	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 93 kb · p 0.011 · regional, not allelic
Overall
CADD	25.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CEP89
Protein: p.Pro357Leu
Coding: c.1070C>T
MANE Select: NM_032816
Type: single nucleotide variant
Location: chr19:32926944 (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.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-pro357leu (accessed [today's date]).

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