Is CFAP300 p.Pro102Ser (c.304C>T) pathogenic?

CFAP300 p.Pro102Ser (c.304C>T) is classified Uncertain significance in CFAP300 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). AlphaMissense: likely benign (0.2212); Very rare (popmax 8.49e-05%, nfe).

How common is CFAP300 p.Pro102Ser (c.304C>T) in the general population?

CFAP300 p.Pro102Ser (c.304C>T) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about CFAP300 p.Pro102Ser (c.304C>T)?

AlphaMissense predicts likely benign (score 0.2212) — an in-silico prediction, not a clinical call.

CFAP300 p.Pro102Ser

c.304C>T · rs2135034140 · VCV1681456

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2212 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2212	likely benign
REVEL	0.47	indeterminate
SaProt	LLR -8.81	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 4.8	GERP 1.8, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 36 kb · p 0.034 · regional, not allelic
Overall
CADD	24.9	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 8.49e-05% European (non-Finnish) · 1/1,178,536 alleles

Overall 6.86e-05% 1/1,457,452 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: CFAP300
Protein: p.Pro102Ser
Coding: c.304C>T
MANE Select: NM_032930
dbSNP: rs2135034140
Type: single nucleotide variant
Location: chr11:102066520 (GRCh38)
Gene constraint: LOEUF 1.386 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.21
Residue 102: 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.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
CFAP300 c.268+13T>C Benign/Likely 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-pro102ser (accessed [today's date]).

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