Is CFAP418 p.Leu166= (c.498A>G) pathogenic?

CFAP418 p.Leu166= (c.498A>G) is classified Conflicting classifications of pathogenicity in CFAP418 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-14). Absent from gnomAD v4.1; Associated with cone-rod dystrophy 16.

What condition is associated with CFAP418 p.Leu166= (c.498A>G)?

CFAP418 p.Leu166= (c.498A>G) is associated with cone-rod dystrophy 16, retinitis pigmentosa (ClinVar).

How common is CFAP418 p.Leu166= (c.498A>G) in the general population?

CFAP418 p.Leu166= (c.498A>G) is absent from gnomAD v4.1 (gnomAD).

How is Cone rod dystrophy inherited?

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

CFAP418 p.Leu166=

c.498A>G · rs1811644695 · VCV913949

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

cone-rod dystrophy 16

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.15	GERP 0.24, phastCons 0.71
Overall
CADD	5.166	PHRED · no single calibrated threshold — expert panels disagree

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.Leu166=
Coding: c.498A>G
MANE Select: NM_177965
dbSNP: rs1811644695
Type: single nucleotide variant
Location: chr8:95247743 (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

cone-rod dystrophy 16 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa

For Cone rod dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

CFAP418 p.Leu166Ter Pathogenic same residue
CFAP418 p.Arg177Trp Pathogenic/Likely pathogenic ★★ same condition
CFAP418 p.Trp147Ter Pathogenic/Likely pathogenic ★★ same condition
CFAP418 c.*408G>A Uncertain significance ★★ same condition
CFAP418 c.*965C>G Uncertain significance ★★ same condition
CFAP418 p.Ala45Gly Uncertain significance ★★ ⚠ same condition
CFAP418 p.Arg177Gln Uncertain significance ★★ ⚠ same condition
CFAP418 p.Arg186Gly 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/cfap418-p-leu166 (accessed [today's date]).

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