Is CFAP410 p.Arg90Pro (c.269G>C) pathogenic?

CFAP410 p.Arg90Pro (c.269G>C) is classified Uncertain significance in CFAP410 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-05). AlphaMissense: likely pathogenic (0.9716); Very rare (popmax 0.00133%, afr); Associated with inherited retinal dystrophy.

What condition is associated with CFAP410 p.Arg90Pro (c.269G>C)?

CFAP410 p.Arg90Pro (c.269G>C) is associated with inherited retinal dystrophy (ClinVar).

How common is CFAP410 p.Arg90Pro (c.269G>C) in the general population?

CFAP410 p.Arg90Pro (c.269G>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CFAP410 p.Arg90Pro (c.269G>C)?

AlphaMissense predicts likely pathogenic (score 0.9716) — an in-silico prediction, not a clinical call.

CFAP410 p.Arg90Pro

c.269G>C · rs567435284 · VCV438158

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9716 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.9716	likely pathogenic · top 10% in CFAP410
REVEL	0.317	indeterminate
SaProt	LLR -15.36	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 1.5, phastCons 0.078
Regional constraint	o/e 1.21	unconstrained · MANE · 8,993 bp · p 8.7e-05 · 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 0.00133% African / African-American · 1/75,056 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000274% 4/1,459,786 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,056
European (non-Finnish)	0.000254%	393,235

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.Arg90Pro
Coding: c.269G>C
MANE Select: NM_004928
dbSNP: rs567435284
Type: single nucleotide variant
Location: chr21:44333137 (GRCh38)
Gene constraint: LOEUF 1.453 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.77 · 1 PDB

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

Disease context

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

Similar variants

CFAP410 p.Arg90Gln Uncertain significance ★★ ⚠ same residue
CFAP410 p.Arg90Trp Uncertain significance ★★ ⚠ same residue
CFAP410 c.96+1G>A Pathogenic ★★ same condition
CFAP410 p.Arg73Pro Pathogenic/Likely pathogenic ★★ ⚠ same condition
CFAP410 p.Pro98Leu Uncertain significance ★★ ⚠ same condition
CFAP410 c.96+6T>A Conflicting classifications of pathogenicity ★ same condition
CFAP410 p.Arg106His Uncertain significance ★ ⚠ same condition
CFAP410 p.Arg108His 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/cfap410-p-arg90pro (accessed [today's date]).

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