Is CFAP418 p.Glu28Lys (c.82G>A) pathogenic?

CFAP418 p.Glu28Lys (c.82G>A) is classified Uncertain significance in CFAP418 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-24). AlphaMissense: likely benign (0.0747); Very rare (popmax 0.00737%, nfe); Associated with bardet-biedl syndrome 21.

What condition is associated with CFAP418 p.Glu28Lys (c.82G>A)?

CFAP418 p.Glu28Lys (c.82G>A) is associated with bardet-biedl syndrome 21, cone-rod dystrophy 16, retinitis pigmentosa (ClinVar).

How common is CFAP418 p.Glu28Lys (c.82G>A) in the general population?

CFAP418 p.Glu28Lys (c.82G>A) is very rare (popmax 0.00737%, nfe) (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.Glu28Lys (c.82G>A)?

AlphaMissense predicts likely benign (score 0.0747) — an in-silico prediction, not a clinical call.

CFAP418 p.Glu28Lys

c.82G>A · rs768222931 · VCV1681153

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0747 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00737%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

bardet-biedl syndrome 21

Computational evidence

Protein change
AlphaMissense	0.0747	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -5.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -0.41, phastCons 0.004
Regional constraint	o/e 1.01	unconstrained · MANE · 22 kb · p 0.91 · regional, not allelic
Overall
CADD	9.226	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00737% European (non-Finnish) · 87/1,180,028 alleles

Filtering AF 0.00605% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00565%

Overall 0.00558% 90/1,614,040 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00737%	13,564
Admixed American	0.00167%	60,010
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-American	0.00133%	74,920

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.Glu28Lys
Coding: c.82G>A
MANE Select: NM_177965
dbSNP: rs768222931
Type: single nucleotide variant
Location: chr8:95269108 (GRCh38)
Gene constraint: LOEUF 1.642 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.73
Residue 28: the 'required for interaction with fam161a' region; the 'disordered' region

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.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
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-glu28lys (accessed [today's date]).

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