Is CIROZ p.Arg113Ter (c.337C>T) pathogenic?

CIROZ p.Arg113Ter (c.337C>T) is classified Conflicting classifications of pathogenicity in CIROZ (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-09-02). Ultra-rare (popmax 0.066%, eas).

How common is CIROZ p.Arg113Ter (c.337C>T) in the general population?

CIROZ p.Arg113Ter (c.337C>T) is ultra-rare (popmax 0.066%, eas) (gnomAD).

CIROZ p.Arg113Ter

c.337C>T · rs558323413 · VCV1335917

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, eas)

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 4 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.4	GERP -0.13
Overall
CADD	29.4	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 0.066% East Asian · 27/40,884 alleles

Filtering AF 0.0466% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0401%

Overall 0.00273% 42/1,536,258 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.066%	1,514
Middle Eastern	0.0167%	5,988
Remaining individualsnot grpmax-eligible	0.005%	19,993
Admixed American	0.00197%	50,836
European (non-Finnish)	0.000872%	114,656

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.Arg113Ter
Coding: c.337C>T
MANE Select: NM_001170754
dbSNP: rs558323413
Type: single nucleotide variant
Location: chr1:10966393 (GRCh38)
Structure: AlphaFold pLDDT 53.62
Residue 113: a UniProt-annotated variant site (in htx14; pathogenic)

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

Similar variants

CIROZ p.Gly689Arg Benign ★★ same type
CIROZ p.Arg732Ter Likely pathogenic ★ same type
CIROZ p.Tyr128Ter Likely pathogenic ★ same type
CIROZ p.Ala750Val Uncertain significance ★ same type
CIROZ p.Gln263Lys Uncertain significance ★ same type
CIROZ p.Gly629Val Uncertain significance ★ same type
CIROZ p.Leu771Ile Uncertain significance ★ same type
CIROZ p.Pro478Ser 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-arg113ter (accessed [today's date]).

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