Is CFAP418 p.Ser150Trp (c.449C>G) pathogenic?

CFAP418 p.Ser150Trp (c.449C>G) is classified Uncertain significance in CFAP418 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-06-13). AlphaMissense: ambiguous (0.5527); Very rare (popmax 0.00502%, amr); Associated with bardet-biedl syndrome 21.

What condition is associated with CFAP418 p.Ser150Trp (c.449C>G)?

CFAP418 p.Ser150Trp (c.449C>G) is associated with bardet-biedl syndrome 21, cone-rod dystrophy 16, retinitis pigmentosa (ClinVar).

How common is CFAP418 p.Ser150Trp (c.449C>G) in the general population?

CFAP418 p.Ser150Trp (c.449C>G) is very rare (popmax 0.00502%, amr) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

What do computational predictors say about CFAP418 p.Ser150Trp (c.449C>G)?

AlphaMissense predicts ambiguous (score 0.5527) — an in-silico prediction, not a clinical call.

CFAP418 p.Ser150Trp

c.449C>G · rs149558233 · VCV1681120

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5527 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00502%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

bardet-biedl syndrome 21

Computational evidence

Protein change
AlphaMissense	0.5527	ambiguous
REVEL	0.719	pathogenic-leaning
SaProt	LLR -15.61	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.47 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 22 kb · p 0.91 · regional, not allelic
Overall
CADD	31.0	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 0.00502% Admixed American · 3/59,800 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000669%

Overall 0.000342% 5/1,460,154 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00502%	19,933
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,576
Remaining individualsnot grpmax-eligible	0.0016%	62,434

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.Ser150Trp
Coding: c.449C>G
MANE Select: NM_177965
dbSNP: rs149558233
Type: single nucleotide variant
Location: chr8:95252209 (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

Also linked: cone-rod dystrophy 16 retinitis pigmentosa

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.Ser150= Conflicting classifications of pathogenicity ★ same residue
CFAP418 p.Ser150Leu Uncertain significance ★ ⚠ 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.Ala178Val Uncertain significance ★★ ⚠ same condition
CFAP418 p.Ala45Gly 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-ser150trp (accessed [today's date]).

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