Is CFAP45 p.Arg451Trp (c.1351C>T) pathogenic?

CFAP45 p.Arg451Trp (c.1351C>T) is classified Uncertain significance in CFAP45 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-21). AlphaMissense: likely benign (0.1253); Ultra-rare (popmax 0.0165%, mid).

How common is CFAP45 p.Arg451Trp (c.1351C>T) in the general population?

CFAP45 p.Arg451Trp (c.1351C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CFAP45 p.Arg451Trp (c.1351C>T)?

AlphaMissense predicts likely benign (score 0.1253) — an in-silico prediction, not a clinical call.

CFAP45 p.Arg451Trp

c.1351C>T · VCV4001505

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1253 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1253	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -12.19	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.35	donor gain · deltas
Pangolin	Δ0.30	gain · loss 0.14 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 28 kb · p 0.64 · regional, not allelic
Overall
CADD	34.0	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 0.0165% Middle Eastern · 1/6,058 alleles

Filtering AF 0.00036% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000261%

Overall 0.000683% 11/1,610,424 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,058
Remaining individualsnot grpmax-eligible	0.0016%	62,372
European (non-Finnish)	0.000765%	130,750

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.Arg451Trp
Coding: c.1351C>T
MANE Select: NM_012337
Type: single nucleotide variant
Location: chr1:159876557 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 2 PDB
Residue 451: the trichohyalin-plectin-homology domain; 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.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
CFAP45 p.Ala69Thr 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-arg451trp (accessed [today's date]).

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