Is CEP85 p.Thr488Ile (c.1463C>T) pathogenic?

CEP85 p.Thr488Ile (c.1463C>T) is classified Uncertain significance in CEP85 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-10). AlphaMissense: likely pathogenic (0.8019); Very rare (popmax 8.48e-05%, nfe).

How common is CEP85 p.Thr488Ile (c.1463C>T) in the general population?

CEP85 p.Thr488Ile (c.1463C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CEP85 p.Thr488Ile (c.1463C>T)?

AlphaMissense predicts likely pathogenic (score 0.8019) — an in-silico prediction, not a clinical call.

CEP85 p.Thr488Ile

c.1463C>T · rs932809281 · VCV2475143

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8019 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8019	likely pathogenic
REVEL	0.24	benign-leaning
SaProt	LLR -14.32	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 38 kb · p 0.075 · regional, not allelic
Overall
CADD	25.8	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 8.48e-05% European (non-Finnish) · 1/1,179,386 alleles

Overall 0.000657% 1/152,226 alleles · very rare

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: CEP85
Protein: p.Thr488Ile
Coding: c.1463C>T
MANE Select: NM_001319944
dbSNP: rs932809281
Type: single nucleotide variant
Location: chr1:26268604 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.09 · 2 PDB

Full CEP85 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP85 p.Ala176= Benign ★★ same type
CEP85 p.Leu405Phe Benign ★★ same type
CEP85 p.Ala374Pro Uncertain significance ★ ⚠ same type
CEP85 p.Ala396Thr Uncertain significance ★ ⚠ same type
CEP85 p.Ala399Ser Uncertain significance ★ ⚠ same type
CEP85 p.Ala656Val Uncertain significance ★ ⚠ same type
CEP85 p.Arg146Lys Uncertain significance ★ ⚠ same type
CEP85 p.Arg177Lys 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/cep85-p-thr488ile (accessed [today's date]).

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