Is CEP78 p.Cys158Phe (c.473G>T) pathogenic?

CEP78 p.Cys158Phe (c.473G>T) is classified Pathogenic/Likely pathogenic in CEP78 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-06-25). AlphaMissense: likely pathogenic (0.9235); Ultra-rare (popmax 0.0124%, amr); Associated with CEP78-related disorder.

What condition is associated with CEP78 p.Cys158Phe (c.473G>T)?

CEP78 p.Cys158Phe (c.473G>T) is associated with CEP78-related disorder, cone-rod dystrophy and hearing loss 1 (ClinVar).

How common is CEP78 p.Cys158Phe (c.473G>T) in the general population?

CEP78 p.Cys158Phe (c.473G>T) is ultra-rare (popmax 0.0124%, amr) (gnomAD).

What do computational predictors say about CEP78 p.Cys158Phe (c.473G>T)?

AlphaMissense predicts likely pathogenic (score 0.9235) — an in-silico prediction, not a clinical call.

CEP78 p.Cys158Phe

c.473G>T · rs754595005 · VCV1058404

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9235 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0124%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CEP78-related disorder

Computational evidence

Protein change
AlphaMissense	0.9235	likely pathogenic ✓ concordant with ClinVar · top 7% in CEP78
REVEL	0.573	indeterminate
SaProt	LLR -14.99	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 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 34 kb · p 0.014 · regional, not allelic
Overall
CADD	29.9	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 0.0124% Admixed American · 7/56,432 alleles

Filtering AF 0.00574% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0041%

Overall 0.000556% 8/1,439,092 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0124%	8,062
Remaining individualsnot grpmax-eligible	0.00162%	61,690

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.Cys158Phe
Coding: c.473G>T
MANE Select: NM_001330691
dbSNP: rs754595005
Type: single nucleotide variant
Location: chr9:78240338 (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

CEP78-related disorder

Also linked: cone-rod dystrophy and hearing loss 1

Similar variants

CEP78 c.1205+2T>A Pathogenic/Likely pathogenic ★★ same condition
CEP78 c.1206-2A>C Pathogenic ★★ same condition
CEP78 c.1206-2A>G Pathogenic/Likely pathogenic ★★ same condition
CEP78 c.1251+5G>A Pathogenic/Likely pathogenic ★★ same condition
CEP78 c.254-1G>T Pathogenic/Likely pathogenic ★★ same condition
CEP78 c.778+1G>A Likely pathogenic ★★ same condition
CEP78 p.Arg483Ter Pathogenic/Likely pathogenic ★★ same condition
CEP78 p.Gln26Ter Pathogenic/Likely 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-cys158phe (accessed [today's date]).

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