Is CFAP418 p.Lys102Ter (c.304A>T) pathogenic?

CFAP418 p.Lys102Ter (c.304A>T) is classified Pathogenic in CFAP418 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-03-28). Very rare (popmax 0.000342%, nfe); Associated with bardet-biedl syndrome 21.

What condition is associated with CFAP418 p.Lys102Ter (c.304A>T)?

CFAP418 p.Lys102Ter (c.304A>T) is associated with bardet-biedl syndrome 21 (ClinVar).

How common is CFAP418 p.Lys102Ter (c.304A>T) in the general population?

CFAP418 p.Lys102Ter (c.304A>T) is very rare (popmax 0.000342%, nfe) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

CFAP418 p.Lys102Ter

c.304A>T · rs766087213 · VCV417789

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000342%, nfe)

Conditions

bardet-biedl syndrome 21

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	predicted	premature termination codon in exon 3 of 6
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Overall
CADD	37.0	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

Grpmax group 0.000342% European (non-Finnish) · 4/1,170,854 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000279% 4/1,435,082 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: CFAP418
Protein: p.Lys102Ter
Coding: c.304A>T
MANE Select: NM_177965
dbSNP: rs766087213
Type: single nucleotide variant
Location: chr8:95260472 (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

bardet-biedl syndrome 21 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Bardet-Biedl syndrome (Orphanet):

Inheritance: Autosomal recessive, Oligogenic
Onset: Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

CFAP418 p.Lys102Glu Uncertain significance ★ ⚠ same residue
CFAP418 p.Arg177Trp Pathogenic/Likely pathogenic ★★ same condition
CFAP418 p.Ala178Val 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
CFAP418 p.Arg201Pro Uncertain significance ★★ ⚠ same condition
CFAP418 p.Cys132Tyr 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-lys102ter (accessed [today's date]).

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