Is CFAP410 p.Cys61Tyr (c.182G>A) pathogenic?

CFAP410 p.Cys61Tyr (c.182G>A) is classified Uncertain significance in CFAP410 (ClinVar, Single submitter, 2 submitters; last evaluated 2016-11-30). AlphaMissense: likely pathogenic (0.9779); Very rare (popmax 8.48e-05%, nfe); Associated with retinal dystrophy with or without macular staphyloma.

What condition is associated with CFAP410 p.Cys61Tyr (c.182G>A)?

CFAP410 p.Cys61Tyr (c.182G>A) is associated with retinal dystrophy with or without macular staphyloma (ClinVar).

How common is CFAP410 p.Cys61Tyr (c.182G>A) in the general population?

CFAP410 p.Cys61Tyr (c.182G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Cone rod dystrophy-short stature syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CFAP410 p.Cys61Tyr (c.182G>A)?

AlphaMissense predicts likely pathogenic (score 0.9779) — an in-silico prediction, not a clinical call.

CFAP410 p.Cys61Tyr

c.182G>A · rs1057518441 · VCV373480

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9779 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

retinal dystrophy with or without macular staphyloma

Computational evidence

Protein change
AlphaMissense	0.9779	likely pathogenic · top 9% in CFAP410
REVEL	0.605	indeterminate
SaProt	LLR -16.28	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 7.5	GERP 1.3, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 8,993 bp · p 8.7e-05 · regional, not allelic
Overall
CADD	28.3	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 8.48e-05% European (non-Finnish) · 1/1,179,848 alleles

Overall 6.85e-05% 1/1,460,412 alleles · very rare

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.Cys61Tyr
Coding: c.182G>A
MANE Select: NM_004928
dbSNP: rs1057518441
Type: single nucleotide variant
Location: chr21:44333224 (GRCh38)
Gene constraint: LOEUF 1.453 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.77 · 1 PDB
Residue 61: a UniProt-annotated variant site (in rdms)

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

Disease context

retinal dystrophy with or without macular staphyloma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Cone rod dystrophy-short stature syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

CFAP410 p.Cys61Gly Uncertain significance ★ ⚠ same residue
CFAP410 c.96+1G>A Pathogenic ★★ same condition
CFAP410 p.Arg73Pro Pathogenic/Likely pathogenic ★★ ⚠ same condition
CFAP410 p.Gln119Ter Pathogenic ★★ same condition
CFAP410 p.Glu96Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
CFAP410 p.Pro116Leu Pathogenic/Likely pathogenic ★★ same condition
CFAP410 p.Pro98Leu Uncertain significance ★★ ⚠ same condition
CFAP410 p.Thr127Met 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/cfap410-p-cys61tyr (accessed [today's date]).

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