Is CIB2 p.Ile7Thr (c.20T>C) pathogenic?

CIB2 p.Ile7Thr (c.20T>C) is classified Uncertain significance in CIB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). AlphaMissense: ambiguous (0.3746); Very rare (popmax 0.00853%, amr); Associated with Inborn genetic diseases.

What condition is associated with CIB2 p.Ile7Thr (c.20T>C)?

CIB2 p.Ile7Thr (c.20T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CIB2 p.Ile7Thr (c.20T>C) in the general population?

CIB2 p.Ile7Thr (c.20T>C) is very rare (popmax 0.00853%, amr) (gnomAD).

What do computational predictors say about CIB2 p.Ile7Thr (c.20T>C)?

AlphaMissense predicts ambiguous (score 0.3746) — an in-silico prediction, not a clinical call.

CIB2 p.Ile7Thr

c.20T>C · VCV3267325

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3746 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00853%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3746	ambiguous
REVEL	0.226	benign-leaning
SaProt	LLR -7.13	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9	GERP 0.62, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 26 kb · p 0.17 · regional, not allelic
Overall
CADD	20.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00853% Admixed American · 5/58,594 alleles

Filtering AF 0.00329% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00211%

Overall 0.000315% 5/1,584,806 alleles · very rare

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: CIB2
Protein: p.Ile7Thr
Coding: c.20T>C
MANE Select: NM_006383
Type: single nucleotide variant
Location: chr15:78131196 (GRCh38)
Gene constraint: LOEUF 1.274 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.71 · 1 PDB
Residue 7: a β-strand

Full CIB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIB2 p.Ala76Val Uncertain significance ★★ ⚠ same condition
CIB2 p.Asn89Ser Uncertain significance ★★ ⚠ same condition
CIB2 p.Asp18His Uncertain significance ★★ ⚠ same condition
CIB2 p.Asp90Asn Uncertain significance ★★ ⚠ same condition
CIB2 p.Gly162Ser Uncertain significance ★★ ⚠ same condition
CIB2 p.Leu158Trp Uncertain significance ★★ ⚠ same condition
CIB2 p.Met44Val Uncertain significance ★★ ⚠ same condition
CIB2 p.Met56Val Uncertain significance ★★ ⚠ 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/cib2-p-ile7thr (accessed [today's date]).

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