Is CIB1 p.Arg72Ter (c.214C>T) pathogenic?

CIB1 p.Arg72Ter (c.214C>T) is classified Pathogenic in CIB1 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-10-14). Ultra-rare (popmax 0.0147%, afr); Associated with epidermodysplasia verruciformis, susceptibility to, 3.

What condition is associated with CIB1 p.Arg72Ter (c.214C>T)?

CIB1 p.Arg72Ter (c.214C>T) is associated with epidermodysplasia verruciformis, susceptibility to, 3 (ClinVar).

How common is CIB1 p.Arg72Ter (c.214C>T) in the general population?

CIB1 p.Arg72Ter (c.214C>T) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

CIB1 p.Arg72Ter

c.214C>T · rs143773090 · VCV599257

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Conditions

epidermodysplasia verruciformis, susceptibility to, 3

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 7
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -1, phastCons 1
Overall
CADD	41.0	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 0.0147% African / African-American · 11/74,928 alleles

Filtering AF 0.00815% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.000805% 13/1,613,948 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,812
European (non-Finnish)	0.000169%	589,981

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: CIB1
Protein: p.Arg72Ter
Coding: c.214C>T
MANE Select: NM_006384
dbSNP: rs143773090
Type: single nucleotide variant
Location: chr15:90231489 (GRCh38)
Gene constraint: LOEUF 1.233 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.37 · 9 PDB
Residue 72: a UniProt-annotated variant site (in ev3; absence of cib1 protein in homozygous patient cells); an α-helix

Full CIB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epidermodysplasia verruciformis, susceptibility to, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIB1 p.Arg72Gln Uncertain significance ★★ ⚠ same residue
CIB1 c.465+1G>A Likely pathogenic ★ same condition
CIB1 c.52-2A>G Pathogenic ★ same condition
CIB1 p.Ala146Thr Likely benign ★ same condition
CIB1 p.Ala184Pro Uncertain significance ★★ ⚠ same type
CIB1 p.Ala66Thr Uncertain significance ★★ ⚠ same type
CIB1 p.Arg113His Uncertain significance ★★ ⚠ same type
CIB1 p.Arg143Gln 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/cib1-p-arg72ter (accessed [today's date]).

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