Is CIROP p.Arg101fs (c.302del) pathogenic?

CIROP p.Arg101fs (c.302del) is classified Likely pathogenic in CIROP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). Ultra-rare (popmax 0.0122%, afr); Associated with heterotaxy, visceral, 12, autosomal.

What condition is associated with CIROP p.Arg101fs (c.302del)?

CIROP p.Arg101fs (c.302del) is associated with heterotaxy, visceral, 12, autosomal (ClinVar).

How common is CIROP p.Arg101fs (c.302del) in the general population?

CIROP p.Arg101fs (c.302del) is ultra-rare (popmax 0.0122%, afr) (gnomAD).

CIROP p.Arg101fs

c.302del · VCV4849971

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, afr)

Conditions

heterotaxy, visceral, 12, 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 1 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.1	GERP -4.4
Overall
CADD	23.5	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 0.0122% African / African-American · 7/57,216 alleles

Filtering AF 0.00567% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00406%

Overall 0.000997% 7/702,272 alleles · ultra-rare exomes 1/550,120 · genomes 6/152,152 · joint denominator

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: CIROP
Protein: p.Arg101fs
Coding: c.302del
MANE Select: NM_001354640
Type: Deletion
Location: chr14:23104619 (GRCh38)
Structure: AlphaFold pLDDT 73.73

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

Disease context

heterotaxy, visceral, 12, autosomal — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIROP p.Gln528Ter Likely pathogenic ★ same condition
CIROP p.Leu444fs Likely pathogenic ★ same condition
CIROP p.Arg22Ter Conflicting classifications of pathogenicity ★ same condition
CIROP p.Gly180Arg Uncertain significance ★ ⚠ same condition
CIROP p.Gly511Glu Uncertain significance ★ ⚠ same condition
CIROP p.Ser31Phe Conflicting classifications of pathogenicity ★ ⚠ same condition
CIROP p.Tyr68Cys Uncertain significance ★ ⚠ same condition
CIROP p.Arg191Ter 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/cirop-p-arg101fs (accessed [today's date]).

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