Is CFAP418 p.Ala2= (c.6G>A) pathogenic?

CFAP418 p.Ala2= (c.6G>A) is classified Likely benign in CFAP418 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-07-18). Very rare (popmax 0.0011%, sas); Associated with CFAP418-related disorder.

What condition is associated with CFAP418 p.Ala2= (c.6G>A)?

CFAP418 p.Ala2= (c.6G>A) is associated with CFAP418-related disorder (ClinVar).

How common is CFAP418 p.Ala2= (c.6G>A) in the general population?

CFAP418 p.Ala2= (c.6G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

CFAP418 p.Ala2=

c.6G>A · VCV3356508

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

CFAP418-related disorder

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 4.7	GERP 1.6, phastCons 1
Overall
CADD	16.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,074 alleles

Overall 0.000205% 3/1,461,760 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,500
Finnishnot grpmax-eligible	0.00156%	64,044
South Asiangrpmax	0.0011%	91,074

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala2=
Coding: c.6G>A
MANE Select: NM_177965
Type: single nucleotide variant
Location: chr8:95269184 (GRCh38)
Gene constraint: LOEUF 1.642 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.73
Residue 2: the 'required for interaction with fam161a' region

Full CFAP418 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CFAP418-related disorder

Similar variants

CFAP418 p.Arg177Trp Pathogenic/Likely pathogenic ★★ same condition
CFAP418 p.Trp147Ter Pathogenic/Likely pathogenic ★★ same condition
CFAP418 p.Ala178Val Uncertain significance ★★ ⚠ same condition
CFAP418 p.Ala45Gly Uncertain significance ★★ ⚠ same condition
CFAP418 c.243+3A>C Likely pathogenic ★ same condition
CFAP418 c.375-1G>C Pathogenic ★ same condition
CFAP418 c.471-1G>T Likely pathogenic ★ same condition
CFAP418 c.374+1G>C Conflicting classifications of pathogenicity ★ 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-ala2 (accessed [today's date]).

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