Is CFAP53 p.Arg231Cys (c.691C>T) pathogenic?

CFAP53 p.Arg231Cys (c.691C>T) is classified Benign/Likely benign in CFAP53 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1175); Common (popmax 46.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with heterotaxy, visceral, 6, autosomal.

What condition is associated with CFAP53 p.Arg231Cys (c.691C>T)?

CFAP53 p.Arg231Cys (c.691C>T) is associated with heterotaxy, visceral, 6, autosomal (ClinVar).

What do computational predictors say about CFAP53 p.Arg231Cys (c.691C>T)?

AlphaMissense predicts likely benign (score 0.1175) — an in-silico prediction, not a clinical call.

CFAP53 p.Arg231Cys

Q: How common is CFAP53 p.Arg231Cys (c.691C>T) in the general population?

CFAP53 p.Arg231Cys (c.691C>T) is common (popmax 46.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.691C>T · rs12607385 · VCV262556

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1175 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 46.7%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

heterotaxy, visceral, 6, autosomal

Computational evidence

Protein change
AlphaMissense	0.1175	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -9.10	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 3.3	GERP 0.49, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 39 kb · p 0.59 · regional, not allelic
Overall
CADD	24.7	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 46.7% East Asian · 20,958/44,866 alleles

Filtering AF 46.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 46%

Overall 2.97% 47,884/1,614,156 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	46.7%	2
Admixed American	23.6%	4
South Asian	5.51%	18
Remaining individualsnot grpmax-eligible	3.75%	27
Finnishnot grpmax-eligible	3.38%	30
Ashkenazi Jewishnot grpmax-eligible	1.85%	54
Middle Eastern	0.94%	106
African / African-American	0.506%	197
European (non-Finnish)	0.192%	520

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.Arg231Cys
Coding: c.691C>T
MANE Select: NM_145020
dbSNP: rs12607385
Type: single nucleotide variant
Location: chr18:50251567 (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 231: 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); a UniProt-annotated variant site (in)

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-arg231cys (accessed [today's date]).

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