Is CFAP53 p.Leu153Pro (c.458T>C) pathogenic?

CFAP53 p.Leu153Pro (c.458T>C) is classified Uncertain significance in CFAP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-31). AlphaMissense: likely pathogenic (0.8535); Very rare (popmax 0.000255%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CFAP53 p.Leu153Pro (c.458T>C)?

CFAP53 p.Leu153Pro (c.458T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CFAP53 p.Leu153Pro (c.458T>C) in the general population?

CFAP53 p.Leu153Pro (c.458T>C) is very rare (popmax 0.000255%, nfe) (gnomAD).

What do computational predictors say about CFAP53 p.Leu153Pro (c.458T>C)?

AlphaMissense predicts likely pathogenic (score 0.8535) — an in-silico prediction, not a clinical call.

CFAP53 p.Leu153Pro

c.458T>C · rs1032384159 · VCV3143552

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8535 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8535	likely pathogenic · top 1% in CFAP53
REVEL	0.163	moderately benign-leaning
SaProt	LLR -16.03	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 8.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 39 kb · p 0.59 · regional, not allelic
Overall
CADD	25.1	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 0.000255% European (non-Finnish) · 3/1,176,348 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000188% 3/1,598,130 alleles · very rare

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.Leu153Pro
Coding: c.458T>C
MANE Select: NM_145020
dbSNP: rs1032384159
Type: single nucleotide variant
Location: chr18:50261079 (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 153: 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-leu153pro (accessed [today's date]).

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