Is CIROP p.Ile411= (c.1233C>T) pathogenic?

CIROP p.Ile411= (c.1233C>T) is classified Likely benign in CIROP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). Ultra-rare (popmax 0.036%, amr).

How common is CIROP p.Ile411= (c.1233C>T) in the general population?

CIROP p.Ile411= (c.1233C>T) is ultra-rare (popmax 0.036%, amr) (gnomAD).

CIROP p.Ile411=

c.1233C>T · rs189668501 · VCV2644089

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.036%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP -1.2, phastCons 1
Overall
CADD	7.489	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.036% Admixed American · 18/49,996 alleles

Filtering AF 0.0232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0192%

Overall 0.00455% 32/702,988 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.036%	2,778
Remaining individualsnot grpmax-eligible	0.00611%	16,360
European (non-Finnish)	0.00312%	32,084

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.Ile411=
Coding: c.1233C>T
MANE Select: NM_001354640
dbSNP: rs189668501
Type: single nucleotide variant
Location: chr14:23102168 (GRCh38)
Structure: AlphaFold pLDDT 73.73
Residue 411: a UniProt-annotated variant site (in htx12)

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

Similar variants

CIROP c.988+1G>C Pathogenic ★ same type
CIROP p.Gln528Ter Likely pathogenic ★ same type
CIROP p.Glu376Lys Likely pathogenic ★ same type
CIROP c.2159+2T>A Uncertain significance ★ same type
CIROP p.Arg22Ter Conflicting classifications of pathogenicity ★ same type
CIROP p.Gly180Arg Uncertain significance ★ ⚠ same type
CIROP p.Gly511Glu Uncertain significance ★ ⚠ same type
CIROP p.Ser31Phe Conflicting classifications of pathogenicity ★ ⚠ 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/cirop-p-ile411 (accessed [today's date]).

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