Is CFAP418 p.Asp20Ala (c.59A>C) pathogenic?

CFAP418 p.Asp20Ala (c.59A>C) is classified Uncertain significance in CFAP418 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-01-01). AlphaMissense: likely benign (0.0998); Absent from gnomAD v4.1; Associated with inherited retinal dystrophy.

What condition is associated with CFAP418 p.Asp20Ala (c.59A>C)?

CFAP418 p.Asp20Ala (c.59A>C) is associated with inherited retinal dystrophy (ClinVar).

How common is CFAP418 p.Asp20Ala (c.59A>C) in the general population?

CFAP418 p.Asp20Ala (c.59A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFAP418 p.Asp20Ala (c.59A>C)?

AlphaMissense predicts likely benign (score 0.0998) — an in-silico prediction, not a clinical call.

CFAP418 p.Asp20Ala

c.59A>C · VCV3250206

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.0998	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -5.86	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 1.5, phastCons 0.98
Regional constraint	o/e 1.01	unconstrained · MANE · 22 kb · p 0.91 · regional, not allelic
Overall
CADD	18.24	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFAP418
Protein: p.Asp20Ala
Coding: c.59A>C
MANE Select: NM_177965
Type: single nucleotide variant
Location: chr8:95269131 (GRCh38)
Gene constraint: LOEUF 1.642 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.73
Residue 20: the 'required for interaction with fam161a' region

Full CFAP418 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

CFAP418 p.Asp20Asn Uncertain significance ★ ⚠ same residue
CFAP418 p.Arg177Trp Pathogenic/Likely pathogenic ★★ same condition
CFAP418 p.Trp147Ter Pathogenic/Likely pathogenic ★★ same condition
CFAP418 p.Glu13Lys Uncertain significance ★★ ⚠ same condition
CFAP418 p.Leu71Phe Uncertain significance ★★ ⚠ same condition
CFAP418 p.Pro106Leu Uncertain significance ★★ ⚠ same condition
CFAP418 p.Ile188= Likely benign ★★ same condition
CFAP418 p.Pro19Ala Benign/Likely benign ★★ ⚠ 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-asp20ala (accessed [today's date]).

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