Is CFAP410 p.Arg73Pro (c.218G>C) pathogenic?

CFAP410 p.Arg73Pro (c.218G>C) is classified Pathogenic/Likely pathogenic in CFAP410 (ClinVar, Multiple submitters, 18 submitters; last evaluated 2026-04-07). AlphaMissense: likely pathogenic (0.816); Ultra-rare (popmax 0.0654%, nfe); Associated with retinal disorder.

What condition is associated with CFAP410 p.Arg73Pro (c.218G>C)?

CFAP410 p.Arg73Pro (c.218G>C) is associated with retinal disorder, cone dystrophy, axial spondylometaphyseal dysplasia (ClinVar).

How common is CFAP410 p.Arg73Pro (c.218G>C) in the general population?

CFAP410 p.Arg73Pro (c.218G>C) is ultra-rare (popmax 0.0654%, nfe) (gnomAD).

What do computational predictors say about CFAP410 p.Arg73Pro (c.218G>C)?

AlphaMissense predicts likely pathogenic (score 0.816) — an in-silico prediction, not a clinical call.

CFAP410 p.Arg73Pro

c.218G>C · rs140451304 · VCV428573

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 18 submitters

AlphaMissense

likely pathogenic

0.816 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0654%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinal disorder

Computational evidence

Protein change
AlphaMissense	0.816	likely pathogenic ✓ concordant with ClinVar
REVEL	0.094	moderately benign-leaning
SaProt	LLR -12.04	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.065	GERP -0.99, phastCons 0.002
Regional constraint	o/e 1.21	unconstrained · MANE · 8,993 bp · p 8.7e-05 · regional, not allelic
Overall
CADD	18.55	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 0.0654% European (non-Finnish) · 772/1,179,884 alleles

Filtering AF 0.0616% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.06%

Overall 0.0502% 810/1,612,638 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0654%	1,528
Remaining individualsnot grpmax-eligible	0.0432%	2,313
African / African-American	0.00801%	12,490
Finnishnot grpmax-eligible	0.00477%	20,960
Admixed American	0.00333%	29,991

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: CFAP410
Protein: p.Arg73Pro
Coding: c.218G>C
MANE Select: NM_004928
dbSNP: rs140451304
Type: single nucleotide variant
Location: chr21:44333188 (GRCh38)
Gene constraint: LOEUF 1.453 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.77 · 1 PDB
Residue 73: a UniProt-annotated variant site (in smdax; patients may exhibit clinical features overlapping with jeune syndrome; decreased function in ciliogenesis; abolishes interaction with nek1)

Full CFAP410 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinal disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cone dystrophy axial spondylometaphyseal dysplasia inherited retinal dystrophy retinitis pigmentosa retinal dystrophy with or without macular staphyloma

Similar variants

CFAP410 p.Arg73His Uncertain significance ★★ ⚠ same residue
CFAP410 p.Arg73Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
CFAP410 p.Arg73Gly Uncertain significance ★ ⚠ same residue
CFAP410 c.545+1G>A Pathogenic ★★ same condition
CFAP410 c.642+2T>C Pathogenic ★★ same condition
CFAP410 c.643-1G>C Pathogenic ★★ same condition
CFAP410 c.643-23A>T Pathogenic/Likely pathogenic ★★ same condition
CFAP410 c.96+1G>A Pathogenic ★★ 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/cfap410-p-arg73pro (accessed [today's date]).

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