Is CEP135 p.Asp455Val (c.1364A>T) pathogenic?

CEP135 p.Asp455Val (c.1364A>T) is classified Conflicting classifications of pathogenicity in CEP135 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2023-07-01). AlphaMissense: likely pathogenic (0.5713); Absent from gnomAD v4.1; Associated with Auditory neuropathy spectrum disorder.

What condition is associated with CEP135 p.Asp455Val (c.1364A>T)?

CEP135 p.Asp455Val (c.1364A>T) is associated with Auditory neuropathy spectrum disorder (ClinVar).

How common is CEP135 p.Asp455Val (c.1364A>T) in the general population?

CEP135 p.Asp455Val (c.1364A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP135 p.Asp455Val (c.1364A>T)?

AlphaMissense predicts likely pathogenic (score 0.5713) — an in-silico prediction, not a clinical call.

CEP135 p.Asp455Val

c.1364A>T · rs1577878190 · VCV694451

Conflicting classifications of pathogenicity No assertion criteria

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.5713 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Auditory neuropathy spectrum disorder

Computational evidence

Protein change
AlphaMissense	0.5713	likely pathogenic
REVEL	0.478	indeterminate
SaProt	LLR -11.41	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 72 kb · p 0.83 · regional, not allelic
Overall
CADD	28.2	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.Asp455Val
Coding: c.1364A>T
MANE Select: NM_025009
dbSNP: rs1577878190
Type: single nucleotide variant
Location: chr4:55974860 (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

Auditory neuropathy spectrum disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP135 c.473-1G>C Likely pathogenic ★★ same type
CEP135 p.Arg1083Ter Pathogenic/Likely pathogenic ★★ same type
CEP135 p.Arg292Ter Pathogenic/Likely pathogenic ★★ same type
CEP135 p.Arg418Ter Pathogenic ★★ same type
CEP135 p.Arg470Ter Pathogenic/Likely pathogenic ★★ same type
CEP135 p.Arg908Ter Pathogenic ★★ same type
CEP135 p.Leu578Ter Pathogenic ★★ same type
CEP135 p.Lys1071Ter Pathogenic/Likely pathogenic ★★ 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/cep135-p-asp455val (accessed [today's date]).

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