Is CFAP53 p.Lys203Arg (c.608A>G) pathogenic?

CFAP53 p.Lys203Arg (c.608A>G) is classified Likely benign in CFAP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-27). AlphaMissense: likely benign (0.0764); Rare (popmax 0.115%, mid); Associated with Inborn genetic diseases.

What condition is associated with CFAP53 p.Lys203Arg (c.608A>G)?

CFAP53 p.Lys203Arg (c.608A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CFAP53 p.Lys203Arg (c.608A>G) in the general population?

CFAP53 p.Lys203Arg (c.608A>G) is rare (popmax 0.115%, mid) (gnomAD).

What do computational predictors say about CFAP53 p.Lys203Arg (c.608A>G)?

AlphaMissense predicts likely benign (score 0.0764) — an in-silico prediction, not a clinical call.

CFAP53 p.Lys203Arg

c.608A>G · rs73962526 · VCV3143555

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0764 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.115%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0764	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -7.01	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 -0.84	GERP -2.8
Regional constraint	o/e 1.02	unconstrained · MANE · 39 kb · p 0.59 · regional, not allelic
Overall
CADD	0.484	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 0.115% Middle Eastern · 7/6,062 alleles

Filtering AF 0.0542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0384%

Overall 0.00496% 80/1,614,216 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.115%	866
African / African-American	0.04%	2,502
Remaining individualsnot grpmax-eligible	0.0256%	3,907
South Asian	0.0121%	8,280
Admixed American	0.00333%	30,008
European (non-Finnish)	0.00119%	84,289

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.Lys203Arg
Coding: c.608A>G
MANE Select: NM_145020
dbSNP: rs73962526
Type: single nucleotide variant
Location: chr18:50251650 (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 203: 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

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-lys203arg (accessed [today's date]).

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