Is CEP43 p.Leu283Pro (c.848T>C) pathogenic?

CEP43 p.Leu283Pro (c.848T>C) is classified Uncertain significance in CEP43 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: likely benign (0.1881); Absent from gnomAD v4.1.

How common is CEP43 p.Leu283Pro (c.848T>C) in the general population?

CEP43 p.Leu283Pro (c.848T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP43 p.Leu283Pro (c.848T>C)?

AlphaMissense predicts likely benign (score 0.1881) — an in-silico prediction, not a clinical call.

CEP43 p.Leu283Pro

c.848T>C · VCV4000957

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1881 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1881	likely benign
REVEL	0.221	benign-leaning
SaProt	LLR -10.24	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 1, phastCons 0.19
Regional constraint	o/e 1.07	unconstrained · MANE · 41 kb · p 0.13 · regional, not allelic
Overall
CADD	22.0	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

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: CEP43
Protein: p.Leu283Pro
Coding: c.848T>C
MANE Select: NM_007045
Type: single nucleotide variant
Location: chr6:167024823 (GRCh38)
Gene constraint: LOEUF 1.163 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.69 · 1 PDB
Residue 283: the 'disordered' region

Full CEP43 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP43 p.Ala148Val Uncertain significance ★ ⚠ same type
CEP43 p.Ala39Gly Uncertain significance ★ ⚠ same type
CEP43 p.Ala6Val Uncertain significance ★ ⚠ same type
CEP43 p.Ala79Glu Uncertain significance ★ ⚠ same type
CEP43 p.Arg112Gln Uncertain significance ★ ⚠ same type
CEP43 p.Arg134Cys Uncertain significance ★ ⚠ same type
CEP43 p.Arg134Gly Uncertain significance ★ ⚠ same type
CEP43 p.Arg17Trp 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/cep43-p-leu283pro (accessed [today's date]).

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