Is CFAP53 p.Ile266= (c.798T>A) pathogenic?

CFAP53 p.Ile266= (c.798T>A) is classified Benign in CFAP53 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-19). Low-frequency (popmax 2.11%, afr); Associated with heterotaxy, visceral, 6, autosomal.

What condition is associated with CFAP53 p.Ile266= (c.798T>A)?

CFAP53 p.Ile266= (c.798T>A) is associated with heterotaxy, visceral, 6, autosomal (ClinVar).

How common is CFAP53 p.Ile266= (c.798T>A) in the general population?

CFAP53 p.Ile266= (c.798T>A) is low-frequency (popmax 2.11%, afr) (gnomAD).

CFAP53 p.Ile266=

c.798T>A · rs113764917 · VCV262559

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.11%, afr)

Conditions

heterotaxy, visceral, 6, autosomal

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.069	GERP -3.5, phastCons 0.48
Overall
CADD	2.347	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.11% African / African-American · 1,584/75,016 alleles

Filtering AF 2.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.99%

Overall 0.12% 1,941/1,614,012 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.11%	47
Middle Eastern	0.248%	403
Remaining individualsnot grpmax-eligible	0.166%	601
Admixed American	0.158%	632
European (non-Finnish)	0.0117%	8,550
South Asian	0.00439%	22,770
Finnishnot grpmax-eligible	0.00156%	64,002

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: CFAP53
Protein: p.Ile266=
Coding: c.798T>A
MANE Select: NM_145020
dbSNP: rs113764917
Type: single nucleotide variant
Location: chr18:50250956 (GRCh38)
Gene constraint: LOEUF 1.282 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.17 · 2 PDB
Residue 266: the trichohyalin-plectin-homology domain; a UniProt-annotated variant site (in htx6; uncertain significance; no overt effects on the structure or function of respiratory cilia)

Full CFAP53 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

heterotaxy, visceral, 6, autosomal — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP53 p.Ala185Thr Uncertain significance ★★ ⚠ same condition
CFAP53 p.Ala385Ser Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg158Gly Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg257Cys Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg505His Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg505Leu Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg505Ser Uncertain significance ★★ ⚠ same condition
CFAP53 p.Asp85Asn 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/cfap53-p-ile266 (accessed [today's date]).

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