Is CFAP53 p.Lys133Asn (c.399A>T) pathogenic?

CFAP53 p.Lys133Asn (c.399A>T) is classified Uncertain significance in CFAP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: ambiguous (0.369); Ultra-rare (popmax 0.0243%, sas); Associated with Inborn genetic diseases.

What condition is associated with CFAP53 p.Lys133Asn (c.399A>T)?

CFAP53 p.Lys133Asn (c.399A>T) is associated with Inborn genetic diseases (ClinVar).

How common is CFAP53 p.Lys133Asn (c.399A>T) in the general population?

CFAP53 p.Lys133Asn (c.399A>T) is ultra-rare (popmax 0.0243%, sas) (gnomAD).

What do computational predictors say about CFAP53 p.Lys133Asn (c.399A>T)?

AlphaMissense predicts ambiguous (score 0.369) — an in-silico prediction, not a clinical call.

CFAP53 p.Lys133Asn

c.399A>T · VCV4614166

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.369 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0243%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.369	ambiguous
REVEL	0.038	moderately benign-leaning
SaProt	LLR -7.54	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.78, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 39 kb · p 0.59 · regional, not allelic
Overall
CADD	22.1	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 0.0243% South Asian · 21/86,278 alleles

Filtering AF 0.0163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00588% 94/1,599,460 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0243%	4,108
Middle Eastern	0.0165%	6,064
Remaining individualsnot grpmax-eligible	0.00806%	12,403
European (non-Finnish)	0.0057%	17,556

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.Lys133Asn
Coding: c.399A>T
MANE Select: NM_145020
Type: single nucleotide variant
Location: chr18:50261138 (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 133: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP53 p.Ala185Thr Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg257Cys Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg470His Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg505His Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg505Leu Uncertain significance ★★ ⚠ same condition
CFAP53 p.Asp85Asn Uncertain significance ★★ ⚠ same condition
CFAP53 p.Cys395Gly Uncertain significance ★★ ⚠ same condition
CFAP53 p.Ala150Thr 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-lys133asn (accessed [today's date]).

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