Is CFAP418 p.Ile97Thr (c.290T>C) pathogenic?

CFAP418 p.Ile97Thr (c.290T>C) is classified Uncertain significance in CFAP418 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). AlphaMissense: likely benign (0.0619); Very rare (popmax 0.00229%, eas); Associated with inherited retinal dystrophy.

What condition is associated with CFAP418 p.Ile97Thr (c.290T>C)?

CFAP418 p.Ile97Thr (c.290T>C) is associated with inherited retinal dystrophy (ClinVar).

How common is CFAP418 p.Ile97Thr (c.290T>C) in the general population?

CFAP418 p.Ile97Thr (c.290T>C) is very rare (popmax 0.00229%, eas) (gnomAD).

What do computational predictors say about CFAP418 p.Ile97Thr (c.290T>C)?

AlphaMissense predicts likely benign (score 0.0619) — an in-silico prediction, not a clinical call.

CFAP418 p.Ile97Thr

c.290T>C · rs1365130476 · VCV3028136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0619 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00229%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.0619	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -4.69	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 5.5	GERP 1.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 22 kb · p 0.91 · regional, not allelic
Overall
CADD	18.31	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

Grpmax group 0.00229% East Asian · 1/43,652 alleles

Overall 0.000139% 2/1,437,640 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00229%	43,652
European (non-Finnish)	8.53e-05%	1,172,633

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.Ile97Thr
Coding: c.290T>C
MANE Select: NM_177965
dbSNP: rs1365130476
Type: single nucleotide variant
Location: chr8:95260486 (GRCh38)
Gene constraint: LOEUF 1.642 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.73

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.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
CFAP418 c.374+1G>A Likely 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/cfap418-p-ile97thr (accessed [today's date]).

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