Is CFAP53 p.Arg471Ter (c.1411C>T) pathogenic?

CFAP53 p.Arg471Ter (c.1411C>T) is classified Uncertain significance in CFAP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-05). Ultra-rare (popmax 0.0165%, mid); Associated with heterotaxy, visceral, 6, autosomal.

What condition is associated with CFAP53 p.Arg471Ter (c.1411C>T)?

CFAP53 p.Arg471Ter (c.1411C>T) is associated with heterotaxy, visceral, 6, autosomal (ClinVar).

How common is CFAP53 p.Arg471Ter (c.1411C>T) in the general population?

CFAP53 p.Arg471Ter (c.1411C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

CFAP53 p.Arg471Ter

c.1411C>T · rs202140882 · VCV1030233

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

heterotaxy, visceral, 6, autosomal

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (8 of 8) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 0.68, phastCons 0.31
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00294%

Overall 0.00378% 61/1,614,100 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.008%	12,500
African / African-American	0.00533%	18,753
European (non-Finnish)	0.00424%	23,600
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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.Arg471Ter
Coding: c.1411C>T
MANE Select: NM_145020
dbSNP: rs202140882
Type: single nucleotide variant
Location: chr18:50227515 (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 471: 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-arg471ter (accessed [today's date]).

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