Is CFAP45 p.Arg511Cys (c.1531C>T) pathogenic?

CFAP45 p.Arg511Cys (c.1531C>T) is classified Uncertain significance in CFAP45 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: likely benign (0.1198); Rare (popmax 0.135%, amr).

How common is CFAP45 p.Arg511Cys (c.1531C>T) in the general population?

CFAP45 p.Arg511Cys (c.1531C>T) is rare (popmax 0.135%, amr) (gnomAD).

What do computational predictors say about CFAP45 p.Arg511Cys (c.1531C>T)?

AlphaMissense predicts likely benign (score 0.1198) — an in-silico prediction, not a clinical call.

CFAP45 p.Arg511Cys

c.1531C>T · VCV4652849

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1198 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.135%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1198	likely benign
REVEL	0.204	benign-leaning
SaProt	LLR -10.18	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.7	GERP 1.2, phastCons 0.96
Regional constraint	o/e 0.98	unconstrained · MANE · 28 kb · p 0.64 · regional, not allelic
Overall
CADD	25.0	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 0.135% Admixed American · 81/60,032 alleles

Filtering AF 0.111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.102%

Overall 0.00644% 104/1,614,240 alleles · rare exomes 51/1,461,884 · genomes 53/152,356 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.135%	741
Remaining individualsnot grpmax-eligible	0.0048%	20,837
African / African-American	0.00266%	37,531
East Asian	0.00223%	44,884
European (non-Finnish)	0.00136%	73,753
South Asian	0.0011%	91,080

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.Arg511Cys
Coding: c.1531C>T
MANE Select: NM_012337
Type: single nucleotide variant
Location: chr1:159872990 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 2 PDB
Residue 511: 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-arg511cys (accessed [today's date]).

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