Is CEP135 p.Asp323Glu (c.969T>A) pathogenic?

CEP135 p.Asp323Glu (c.969T>A) is classified Uncertain significance in CEP135 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-10). AlphaMissense: likely pathogenic (0.793); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CEP135 p.Asp323Glu (c.969T>A)?

CEP135 p.Asp323Glu (c.969T>A) is associated with Inborn genetic diseases (ClinVar).

How common is CEP135 p.Asp323Glu (c.969T>A) in the general population?

CEP135 p.Asp323Glu (c.969T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP135 p.Asp323Glu (c.969T>A)?

AlphaMissense predicts likely pathogenic (score 0.793) — an in-silico prediction, not a clinical call.

CEP135 p.Asp323Glu

c.969T>A · VCV3266019

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.793 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.793	likely pathogenic · top 6% in CEP135
REVEL	0.269	benign-leaning
SaProt	LLR -4.34	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.59	GERP 1.1, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 72 kb · p 0.83 · regional, not allelic
Overall
CADD	21.0	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: CEP135
Protein: p.Asp323Glu
Coding: c.969T>A
MANE Select: NM_025009
Type: single nucleotide variant
Location: chr4:55965784 (GRCh38)
Gene constraint: LOEUF 0.989 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.15 · 2 PDB

Full CEP135 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP135 p.Asp323Asn Uncertain significance ★ ⚠ same residue
CEP135 p.Leu578Ter Pathogenic ★★ same condition
CEP135 c.2617-3C>T Uncertain significance ★★ same condition
CEP135 p.Ala1038Gly Uncertain significance ★★ ⚠ same condition
CEP135 p.Arg1116Gln Uncertain significance ★★ ⚠ same condition
CEP135 p.Arg168Cys Uncertain significance ★★ ⚠ same condition
CEP135 p.Arg252Trp Uncertain significance ★★ ⚠ same condition
CEP135 p.Arg435Cys Uncertain significance ★★ ⚠ same condition

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/cep135-p-asp323glu (accessed [today's date]).

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