Is CFAP53 p.Lys331= (c.993A>G) pathogenic?

CFAP53 p.Lys331= (c.993A>G) is classified Likely benign in CFAP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). Ultra-rare (popmax 0.0493%, mid); Associated with heterotaxy, visceral, 6, autosomal.

What condition is associated with CFAP53 p.Lys331= (c.993A>G)?

CFAP53 p.Lys331= (c.993A>G) is associated with heterotaxy, visceral, 6, autosomal (ClinVar).

How common is CFAP53 p.Lys331= (c.993A>G) in the general population?

CFAP53 p.Lys331= (c.993A>G) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

CFAP53 p.Lys331=

c.993A>G · rs780902052 · VCV2848245

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

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 0.63	GERP -0.37, phastCons 0.99
Overall
CADD	8.052	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00715%

Overall 0.00229% 37/1,613,776 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
Admixed American	0.01%	9,997
Remaining individualsnot grpmax-eligible	0.0064%	15,620
European (non-Finnish)	0.00203%	49,161

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.Lys331=
Coding: c.993A>G
MANE Select: NM_145020
dbSNP: rs780902052
Type: single nucleotide variant
Location: chr18:50250761 (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 331: 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.Lys331Arg Uncertain significance ★ ⚠ 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.Arg505His Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg505Leu Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg505Ser 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-lys331 (accessed [today's date]).

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