Is CEP78 p.Val475fs (c.1424del) pathogenic?

CEP78 p.Val475fs (c.1424del) is classified Pathogenic/Likely pathogenic in CEP78 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-01-18). Very rare (popmax 0.000699%, nfe); Associated with cone-rod dystrophy and hearing loss 1.

What condition is associated with CEP78 p.Val475fs (c.1424del)?

CEP78 p.Val475fs (c.1424del) is associated with cone-rod dystrophy and hearing loss 1, cone-rod dystrophy (ClinVar).

How common is CEP78 p.Val475fs (c.1424del) in the general population?

CEP78 p.Val475fs (c.1424del) is very rare (popmax 0.000699%, nfe) (gnomAD).

CEP78 p.Val475fs

c.1424del · rs1196886096 · VCV813161

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000699%, nfe)

Conditions

cone-rod dystrophy and hearing loss 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP -1.2, phastCons 1
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000699% European (non-Finnish) · 8/1,144,410 alleles

Filtering AF 0.000301% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000217%

Overall 0.000517% 8/1,547,130 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: CEP78
Protein: p.Val475fs
Coding: c.1424del
MANE Select: NM_001330691
dbSNP: rs1196886096
Type: Deletion
Location: chr9:78262950 (GRCh38)
Gene constraint: LOEUF 1.531 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.28

Full CEP78 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cone-rod dystrophy and hearing loss 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cone-rod dystrophy

Similar variants

CEP78 p.Lys179fs Pathogenic ★★ same condition
CEP78 p.Ser485fs Pathogenic/Likely pathogenic ★★ same condition
CEP78 p.Ser567fs Pathogenic/Likely pathogenic ★★ same condition
CEP78 p.Trp212fs Pathogenic ★★ same condition
CEP78 p.Pro587fs Likely pathogenic ★ same condition
CEP78 p.Val475Gly Uncertain significance ★ ⚠ same residue
CEP78 c.1205+2T>A Pathogenic/Likely pathogenic ★★ same condition
CEP78 c.1206-2A>C Pathogenic ★★ 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/cep78-p-val475fs (accessed [today's date]).

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