Is CFAP53 p.Lys375= (c.1125G>A) pathogenic?

CFAP53 p.Lys375= (c.1125G>A) is classified Likely benign in CFAP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). Rare (popmax 0.103%, afr); Associated with heterotaxy, visceral, 6, autosomal.

What condition is associated with CFAP53 p.Lys375= (c.1125G>A)?

CFAP53 p.Lys375= (c.1125G>A) is associated with heterotaxy, visceral, 6, autosomal (ClinVar).

How common is CFAP53 p.Lys375= (c.1125G>A) in the general population?

CFAP53 p.Lys375= (c.1125G>A) is rare (popmax 0.103%, afr) (gnomAD).

CFAP53 p.Lys375=

c.1125G>A · rs372566333 · VCV711447

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.103%, 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 1.4	GERP 0.79, phastCons 1
Overall
CADD	9.857	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.103% African / African-American · 77/75,042 alleles

Filtering AF 0.0841% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0773%

Overall 0.00576% 93/1,614,060 alleles · rare exomes 51/1,461,774 · genomes 42/152,286 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.103%	975
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Admixed American	0.0117%	8,573
South Asian	0.0011%	91,082

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.Lys375=
Coding: c.1125G>A
MANE Select: NM_145020
dbSNP: rs372566333
Type: single nucleotide variant
Location: chr18:50242988 (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 375: 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-lys375 (accessed [today's date]).

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