Is CFAP300 p.Arg252Cys (c.754C>T) pathogenic?

CFAP300 p.Arg252Cys (c.754C>T) is classified Benign in CFAP300 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: ambiguous (0.3563); Ultra-rare (popmax 0.0341%, mid).

How common is CFAP300 p.Arg252Cys (c.754C>T) in the general population?

CFAP300 p.Arg252Cys (c.754C>T) is ultra-rare (popmax 0.0341%, mid) (gnomAD).

What do computational predictors say about CFAP300 p.Arg252Cys (c.754C>T)?

AlphaMissense predicts ambiguous (score 0.3563) — an in-silico prediction, not a clinical call.

CFAP300 p.Arg252Cys

c.754C>T · rs199754694 · VCV1681470

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3563 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0341%, mid)

Computational evidence

Protein change
AlphaMissense	0.3563	ambiguous
REVEL	0.402	indeterminate
SaProt	LLR -9.35	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.27	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 36 kb · p 0.034 · regional, not allelic
Overall
CADD	28.9	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 0.0341% Middle Eastern · 2/5,870 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.0434% 680/1,565,560 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.798%	125
Middle Easterngrpmax	0.0341%	2,935
Remaining individualsnot grpmax-eligible	0.0316%	3,167
European (non-Finnish)	0.0139%	7,208
South Asian	0.00609%	16,418

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg252Cys
Coding: c.754C>T
MANE Select: NM_032930
dbSNP: rs199754694
Type: single nucleotide variant
Location: chr11:102083149 (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

Similar variants

CFAP300 p.Arg252His Uncertain significance ★ ⚠ same residue
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
CFAP300 c.110+16A>G Benign ★★ same type
CFAP300 c.192+59A>C Benign ★★ 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-arg252cys (accessed [today's date]).

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