Is CFAP45 p.Arg350Ter (c.1048C>T) pathogenic?

CFAP45 p.Arg350Ter (c.1048C>T) is classified Likely pathogenic in CFAP45 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). Ultra-rare (popmax 0.025%, amr); Associated with heterotaxy, visceral, 11, autosomal, with male infertility.

What condition is associated with CFAP45 p.Arg350Ter (c.1048C>T)?

CFAP45 p.Arg350Ter (c.1048C>T) is associated with heterotaxy, visceral, 11, autosomal, with male infertility (ClinVar).

How common is CFAP45 p.Arg350Ter (c.1048C>T) in the general population?

CFAP45 p.Arg350Ter (c.1048C>T) is ultra-rare (popmax 0.025%, amr) (gnomAD).

CFAP45 p.Arg350Ter

c.1048C>T · VCV4850564

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, amr)

Conditions

heterotaxy, visceral, 11, autosomal, with male infertility

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 12
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.3, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.025% Admixed American · 15/59,988 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.0054% 87/1,611,844 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.025%	3,999
East Asian	0.00668%	14,961
European (non-Finnish)	0.00543%	18,407
Remaining individualsnot grpmax-eligible	0.0032%	31,212
South Asian	0.0022%	45,524
Finnishnot grpmax-eligible	0.00156%	64,008

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.Arg350Ter
Coding: c.1048C>T
MANE Select: NM_012337
Type: single nucleotide variant
Location: chr1:159877459 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 2 PDB
Residue 350: 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

Disease context

heterotaxy, visceral, 11, autosomal, with male infertility — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP45 p.Lys518Glu Uncertain significance ★★ ⚠ same condition
CFAP45 p.Arg303Ter Pathogenic same condition
CFAP45 p.Gln241Ter Pathogenic same condition
CFAP45 p.Gln491fs Pathogenic ★ same condition
CFAP45 p.Gln151fs Pathogenic same condition
CFAP45 p.Asp320Tyr Uncertain significance ★★ ⚠ same type
CFAP45 p.Asp222Gly Benign ★★ ⚠ same type
CFAP45 p.Ala15Pro 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-arg350ter (accessed [today's date]).

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