Is CFAP45 p.Arg480Cys (c.1438C>T) pathogenic?

CFAP45 p.Arg480Cys (c.1438C>T) is classified Uncertain significance in CFAP45 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-21). AlphaMissense: likely benign (0.1069); Very rare (popmax 0.01%, nfe).

How common is CFAP45 p.Arg480Cys (c.1438C>T) in the general population?

CFAP45 p.Arg480Cys (c.1438C>T) is very rare (popmax 0.01%, nfe) (gnomAD).

What do computational predictors say about CFAP45 p.Arg480Cys (c.1438C>T)?

AlphaMissense predicts likely benign (score 0.1069) — an in-silico prediction, not a clinical call.

CFAP45 p.Arg480Cys

c.1438C>T · rs367766458 · VCV2382412

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1069 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1069	likely benign
REVEL	0.177	moderately benign-leaning
SaProt	LLR -9.36	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 3.9	GERP -0.69, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 28 kb · p 0.64 · regional, not allelic
Overall
CADD	25.2	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 0.01% European (non-Finnish) · 118/1,180,032 alleles

Filtering AF 0.00851% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00795%

Overall 0.00818% 132/1,614,056 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.01%	10,000
African / African-American	0.00801%	12,488
Remaining individualsnot grpmax-eligible	0.0064%	15,622
East Asian	0.00223%	44,876
South Asian	0.0022%	45,544
Admixed American	0.00167%	60,012

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: CFAP45
Protein: p.Arg480Cys
Coding: c.1438C>T
MANE Select: NM_012337
dbSNP: rs367766458
Type: single nucleotide variant
Location: chr1:159873083 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 2 PDB
Residue 480: the trichohyalin-plectin-homology domain; the 'disordered' region; a UniProt-annotated variant site (in htx11; loss of panaxonemal expression in respiratory cilia and in sperm flagella)

Full CFAP45 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP45 p.Arg480Pro Uncertain significance ★ ⚠ same residue
CFAP45 p.Asp320Tyr Uncertain significance ★★ ⚠ same type
CFAP45 p.Lys518Glu Uncertain significance ★★ ⚠ same type
CFAP45 p.Asp222Gly Benign ★★ ⚠ same type
CFAP45 p.Arg350Ter Likely pathogenic ★ same type
CFAP45 p.Ala15Pro Uncertain significance ★ ⚠ same type
CFAP45 p.Ala370Pro Uncertain significance ★ ⚠ same type
CFAP45 p.Ala436Val Uncertain significance ★ ⚠ 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/cfap45-p-arg480cys (accessed [today's date]).

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