Is CIROP p.Arg191Ter (c.571C>T) pathogenic?

CIROP p.Arg191Ter (c.571C>T) is classified Pathogenic in CIROP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-03-15). Very rare (popmax 0.00699%, afr); Associated with heterotaxy, visceral, 12, autosomal.

What condition is associated with CIROP p.Arg191Ter (c.571C>T)?

CIROP p.Arg191Ter (c.571C>T) is associated with heterotaxy, visceral, 12, autosomal (ClinVar).

How common is CIROP p.Arg191Ter (c.571C>T) in the general population?

CIROP p.Arg191Ter (c.571C>T) is very rare (popmax 0.00699%, afr) (gnomAD).

CIROP p.Arg191Ter

c.571C>T · rs764530848 · VCV1344495

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00699%, afr)

Conditions

heterotaxy, visceral, 12, autosomal

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 16
Splicing
SpliceAI	Δ0.37	donor loss, 32 bp away · masked 0 · deltas
Pangolin	Δ0.45	loss · gain 0.11 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.4	GERP -1.3, phastCons 0.51
Overall
CADD	32.0	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 0.00699% African / African-American · 4/57,258 alleles

Filtering AF 0.00233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0014%

Overall 0.00157% 11/702,850 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00699%	14,315
South Asian	0.00592%	16,898
European (non-Finnish)	0.000779%	128,324

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.Arg191Ter
Coding: c.571C>T
MANE Select: NM_001354640
dbSNP: rs764530848
Type: single nucleotide variant
Location: chr14:23103707 (GRCh38)
Structure: AlphaFold pLDDT 73.73
Residue 191: a UniProt-annotated variant site (in htx12)

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.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.Arg389Ile Pathogenic same condition
CIROP p.Ser384Leu 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-arg191ter (accessed [today's date]).

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