Is CFAP418 p.Leu166Ter (c.497T>A) pathogenic?

CFAP418 p.Leu166Ter (c.497T>A) is classified Pathogenic in CFAP418 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2012-01-13). Absent from gnomAD v4.1; Associated with retinitis pigmentosa 64.

What condition is associated with CFAP418 p.Leu166Ter (c.497T>A)?

CFAP418 p.Leu166Ter (c.497T>A) is associated with retinitis pigmentosa 64 (ClinVar).

How common is CFAP418 p.Leu166Ter (c.497T>A) in the general population?

CFAP418 p.Leu166Ter (c.497T>A) is absent from gnomAD v4.1 (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CFAP418 p.Leu166Ter

c.497T>A · rs1064792852 · VCV31192

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

retinitis pigmentosa 64

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.32	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Overall
CADD	38.0	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

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: CFAP418
Protein: p.Leu166Ter
Coding: c.497T>A
MANE Select: NM_177965
dbSNP: rs1064792852
Type: single nucleotide variant
Location: chr8:95247744 (GRCh38)
Gene constraint: LOEUF 1.642 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.73

Full CFAP418 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa 64 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

CFAP418 p.Leu166= Conflicting classifications of pathogenicity ★ same residue
CFAP418 p.Trp185Ter Pathogenic/Likely pathogenic ★★ same condition
CFAP418 c.244-2A>C Pathogenic/Likely pathogenic same condition
CFAP418 p.Gln182Arg Pathogenic same condition
CFAP418 p.Arg177Trp Pathogenic/Likely pathogenic ★★ same type
CFAP418 p.Trp147Ter Pathogenic/Likely pathogenic ★★ same type
CFAP418 c.*408G>A Uncertain significance ★★ same type
CFAP418 c.*965C>G 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/cfap418-p-leu166ter (accessed [today's date]).

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