Is CFAP53 p.Arg505Ser (c.1513C>A) pathogenic?

CFAP53 p.Arg505Ser (c.1513C>A) is classified Uncertain significance in CFAP53 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-25). AlphaMissense: likely pathogenic (0.8013); Ultra-rare (popmax 0.0653%, nfe); Associated with heterotaxy, visceral, 6, autosomal.

What condition is associated with CFAP53 p.Arg505Ser (c.1513C>A)?

CFAP53 p.Arg505Ser (c.1513C>A) is associated with heterotaxy, visceral, 6, autosomal (ClinVar).

How common is CFAP53 p.Arg505Ser (c.1513C>A) in the general population?

CFAP53 p.Arg505Ser (c.1513C>A) is ultra-rare (popmax 0.0653%, nfe) (gnomAD).

What do computational predictors say about CFAP53 p.Arg505Ser (c.1513C>A)?

AlphaMissense predicts likely pathogenic (score 0.8013) — an in-silico prediction, not a clinical call.

CFAP53 p.Arg505Ser

c.1513C>A · rs192619553 · VCV1953801

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8013 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0653%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

heterotaxy, visceral, 6, autosomal

Computational evidence

Protein change
AlphaMissense	0.8013	likely pathogenic · top 1% in CFAP53
REVEL	0.253	benign-leaning
SaProt	LLR -5.99	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.5	GERP -3, phastCons 0.99
Regional constraint	o/e 1.02	unconstrained · MANE · 39 kb · p 0.59 · regional, not allelic
Overall
CADD	19.75	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0653% European (non-Finnish) · 770/1,179,896 alleles

Filtering AF 0.0614% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0599%

Overall 0.0527% 851/1,614,050 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0653%	1,532
Remaining individualsnot grpmax-eligible	0.0624%	1,603
Admixed American	0.0317%	3,159
African / African-American	0.016%	6,255
Finnishnot grpmax-eligible	0.0156%	6,405
South Asian	0.0011%	91,074

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.Arg505Ser
Coding: c.1513C>A
MANE Select: NM_145020
dbSNP: rs192619553
Type: single nucleotide variant
Location: chr18:50227413 (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 505: 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.Arg505His Uncertain significance ★★ ⚠ same residue
CFAP53 p.Arg505Leu Uncertain significance ★★ ⚠ same residue
CFAP53 p.Arg505Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
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.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-arg505ser (accessed [today's date]).

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