Is CIROZ p.Gln404fs (c.1210del) pathogenic?

CIROZ p.Gln404fs (c.1210del) is classified Pathogenic in CIROZ (ClinVar, Single submitter, 2 submitters; last evaluated 2026-07-31). Very rare (popmax 0.00857%, amr); Associated with heterotaxy, visceral, 14, autosomal.

What condition is associated with CIROZ p.Gln404fs (c.1210del)?

CIROZ p.Gln404fs (c.1210del) is associated with heterotaxy, visceral, 14, autosomal (ClinVar).

How common is CIROZ p.Gln404fs (c.1210del) in the general population?

CIROZ p.Gln404fs (c.1210del) is very rare (popmax 0.00857%, amr) (gnomAD).

CIROZ p.Gln404fs

c.1210del · VCV3602008

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00857%, amr)

Conditions

heterotaxy, visceral, 14, autosomal

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 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.6	GERP -3
Overall
CADD	22.0	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 0.00857% Admixed American · 5/58,348 alleles

Filtering AF 0.00333% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00212%

Overall 0.000562% 9/1,602,018 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00857%	11,670
European (non-Finnish)	0.000341%	293,647

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: CIROZ
Protein: p.Gln404fs
Coding: c.1210del
MANE Select: NM_001170754
Type: Deletion
Location: chr1:10949704 (GRCh38)
Structure: AlphaFold pLDDT 53.62
Residue 404: a UniProt-annotated variant site (in htx14; pathogenic); the 'disordered' region

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

Disease context

heterotaxy, visceral, 14, autosomal — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIROZ p.Arg732Ter Likely pathogenic ★ same condition
CIROZ p.Tyr128Ter Likely pathogenic ★ same condition
CIROZ p.Thr19Met Uncertain significance ★ same condition
CIROZ p.Arg193Ter Pathogenic same condition
CIROZ p.Leu798fs 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/ciroz-p-gln404fs (accessed [today's date]).

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