Is CFAP53 p.Trp205Cys (c.615G>C) pathogenic?

CFAP53 p.Trp205Cys (c.615G>C) is classified Benign in CFAP53 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-19). AlphaMissense: likely pathogenic (0.8312); Low-frequency (popmax 2.11%, afr); Associated with heterotaxy, visceral, 6, autosomal.

What condition is associated with CFAP53 p.Trp205Cys (c.615G>C)?

CFAP53 p.Trp205Cys (c.615G>C) is associated with heterotaxy, visceral, 6, autosomal (ClinVar).

How common is CFAP53 p.Trp205Cys (c.615G>C) in the general population?

CFAP53 p.Trp205Cys (c.615G>C) is low-frequency (popmax 2.11%, afr) (gnomAD).

What do computational predictors say about CFAP53 p.Trp205Cys (c.615G>C)?

AlphaMissense predicts likely pathogenic (score 0.8312) — an in-silico prediction, not a clinical call.

CFAP53 p.Trp205Cys

c.615G>C · rs113161381 · VCV262555

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8312 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.11%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

heterotaxy, visceral, 6, autosomal

Computational evidence

Protein change
AlphaMissense	0.8312	likely pathogenic · top 1% in CFAP53
REVEL	0.189	benign-leaning
SaProt	LLR -10.34	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 39 kb · p 0.59 · regional, not allelic
Overall
CADD	26.0	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 2.11% African / African-American · 1,583/75,042 alleles

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

Overall 0.119% 1,913/1,614,200 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.11%	47
Middle Eastern	0.198%	505
Remaining individualsnot grpmax-eligible	0.158%	631
Admixed American	0.157%	638
European (non-Finnish)	0.0102%	9,834
South Asian	0.00439%	22,772
Finnishnot grpmax-eligible	0.00156%	64,040

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.Trp205Cys
Coding: c.615G>C
MANE Select: NM_145020
dbSNP: rs113161381
Type: single nucleotide variant
Location: chr18:50251643 (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 205: 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-trp205cys (accessed [today's date]).

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