Is CFAP53 p.Arg350His (c.1049G>A) pathogenic?

CFAP53 p.Arg350His (c.1049G>A) is classified Uncertain significance in CFAP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-16). AlphaMissense: likely benign (0.075); Ultra-rare (popmax 0.056%, sas); Associated with Inborn genetic diseases.

What condition is associated with CFAP53 p.Arg350His (c.1049G>A)?

CFAP53 p.Arg350His (c.1049G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CFAP53 p.Arg350His (c.1049G>A) in the general population?

CFAP53 p.Arg350His (c.1049G>A) is ultra-rare (popmax 0.056%, sas) (gnomAD).

What do computational predictors say about CFAP53 p.Arg350His (c.1049G>A)?

AlphaMissense predicts likely benign (score 0.075) — an in-silico prediction, not a clinical call.

CFAP53 p.Arg350His

c.1049G>A · rs371352284 · VCV3143539

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.075 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.056%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.075	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -8.43	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 -3.8	GERP -3.5
Regional constraint	o/e 1.02	unconstrained · MANE · 39 kb · p 0.59 · regional, not allelic
Overall
CADD	12.22	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.056% South Asian · 51/91,076 alleles

Filtering AF 0.0437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0394%

Overall 0.00707% 114/1,613,454 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.056%	1,786
Finnishnot grpmax-eligible	0.0345%	2,899
Middle Eastern	0.0329%	3,042
African / African-American	0.00801%	12,484
Remaining individualsnot grpmax-eligible	0.008%	12,497
European (non-Finnish)	0.00229%	43,694
Admixed American	0.00167%	60,004

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.Arg350His
Coding: c.1049G>A
MANE Select: NM_145020
dbSNP: rs371352284
Type: single nucleotide variant
Location: chr18:50243064 (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 350: 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.Arg350Cys Uncertain significance ★ ⚠ same residue
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

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-arg350his (accessed [today's date]).

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