Is CFAP300 p.Arg252His (c.755G>A) pathogenic?

CFAP300 p.Arg252His (c.755G>A) is classified Uncertain significance in CFAP300 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely benign (0.215); Very rare (popmax 0.00703%, eas); Associated with Inborn genetic diseases.

What condition is associated with CFAP300 p.Arg252His (c.755G>A)?

CFAP300 p.Arg252His (c.755G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CFAP300 p.Arg252His (c.755G>A) in the general population?

CFAP300 p.Arg252His (c.755G>A) is very rare (popmax 0.00703%, eas) (gnomAD).

What do computational predictors say about CFAP300 p.Arg252His (c.755G>A)?

AlphaMissense predicts likely benign (score 0.215) — an in-silico prediction, not a clinical call.

CFAP300 p.Arg252His

c.755G>A · rs528406781 · VCV3143448

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.215 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00703%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.215	likely benign
REVEL	0.442	indeterminate
SaProt	LLR -8.73	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 36 kb · p 0.034 · regional, not allelic
Overall
CADD	25.5	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 0.00703% East Asian · 3/42,696 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00301%

Overall 0.00416% 65/1,563,982 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00703%	14,232
African / African-American	0.00545%	18,337
Admixed American	0.00532%	18,783
Remaining individualsnot grpmax-eligible	0.00499%	20,040
European (non-Finnish)	0.00434%	23,051
Finnishnot grpmax-eligible	0.00162%	61,784
South Asian	0.00122%	81,918

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: CFAP300
Protein: p.Arg252His
Coding: c.755G>A
MANE Select: NM_032930
dbSNP: rs528406781
Type: single nucleotide variant
Location: chr11:102083150 (GRCh38)
Gene constraint: LOEUF 1.386 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.21
Residue 252: a UniProt-annotated variant site (in cild38; loss of ciliary axoneme inner dynein arm and outer dynein arm structures in patient respiratory epithelial cells)

Full CFAP300 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

CFAP300 p.Arg252Cys Benign ★ ⚠ same residue
CFAP300 p.Glu239Asp Uncertain significance ★ ⚠ same condition
CFAP300 p.Phe14Cys Uncertain significance ★ ⚠ same condition
CFAP300 p.Arg121Ter Pathogenic ★★ same type
CFAP300 p.Arg144Ter Pathogenic/Likely pathogenic ★★ same type
CFAP300 p.Gln160Ter Pathogenic ★★ same type
CFAP300 p.Gln52Ter Pathogenic ★★ same type
CFAP300 p.His259Arg Pathogenic/Likely pathogenic ★★ same type

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/cfap300-p-arg252his (accessed [today's date]).

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