Is CFAP45 p.Gln491fs (c.1472_1477delinsT) pathogenic?

CFAP45 p.Gln491fs (c.14721477delinsT) is classified Pathogenic in CFAP45 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-01-20). Absent from gnomAD; Associated with heterotaxy, visceral, 11, autosomal, with male infertility.

What condition is associated with CFAP45 p.Gln491fs (c.1472_1477delinsT)?

CFAP45 p.Gln491fs (c.1472_1477delinsT) is associated with heterotaxy, visceral, 11, autosomal, with male infertility (ClinVar).

How common is CFAP45 p.Gln491fs (c.1472_1477delinsT) in the general population?

CFAP45 p.Gln491fs (c.1472_1477delinsT) is absent from gnomAD (gnomAD).

CFAP45 p.Gln491fs

c.1472_1477delinsT · rs2101839185 · VCV1319990

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP 2.4, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CFAP45
Protein: p.Gln491fs
Coding: c.1472_1477delinsT
MANE Select: NM_012337
dbSNP: rs2101839185
Type: Indel
Location: chr1:159873044 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 2 PDB
Residue 491: 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.Arg350Ter Likely pathogenic ★ same condition
CFAP45 p.Arg303Ter Pathogenic same condition
CFAP45 p.Gln151fs Pathogenic same condition
CFAP45 p.Gln241Ter Pathogenic same condition

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-gln491fs (accessed [today's date]).

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