Is CFAP418 p.Ala178Val (c.533C>T) pathogenic?

CFAP418 p.Ala178Val (c.533C>T) is classified Uncertain significance in CFAP418 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-08-16). AlphaMissense: likely pathogenic (0.8431); Ultra-rare (popmax 0.0879%, sas); Associated with CFAP418-related disorder.

What condition is associated with CFAP418 p.Ala178Val (c.533C>T)?

CFAP418 p.Ala178Val (c.533C>T) is associated with CFAP418-related disorder, bardet-biedl syndrome 21 (ClinVar).

How common is CFAP418 p.Ala178Val (c.533C>T) in the general population?

CFAP418 p.Ala178Val (c.533C>T) is ultra-rare (popmax 0.0879%, sas) (gnomAD).

What do computational predictors say about CFAP418 p.Ala178Val (c.533C>T)?

AlphaMissense predicts likely pathogenic (score 0.8431) — an in-silico prediction, not a clinical call.

CFAP418 p.Ala178Val

c.533C>T · rs375314973 · VCV430653

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.8431 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0879%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CFAP418-related disorder

Computational evidence

Protein change
AlphaMissense	0.8431	likely pathogenic
REVEL	0.817	moderately pathogenic-leaning
SaProt	LLR -10.42	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
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	27.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0879% South Asian · 80/91,034 alleles

Filtering AF 0.0723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0666%

Overall 0.00843% 136/1,613,680 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0879%	1,138
Remaining individualsnot grpmax-eligible	0.0048%	20,827
European (non-Finnish)	0.00441%	22,690
African / African-American	0.00134%	74,842

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.Ala178Val
Coding: c.533C>T
MANE Select: NM_177965
dbSNP: rs375314973
Type: single nucleotide variant
Location: chr8:95247708 (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

CFAP418-related disorder

Also linked: bardet-biedl syndrome 21

Similar variants

CFAP418 p.Ala178= Likely benign ★ same residue
CFAP418 p.Arg177Trp Pathogenic/Likely pathogenic ★★ same condition
CFAP418 p.Trp147Ter Pathogenic/Likely pathogenic ★★ 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-ala178val (accessed [today's date]).

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