Is CIB1 p.Ala82Pro (c.244G>C) pathogenic?

CIB1 p.Ala82Pro (c.244G>C) is classified Uncertain significance in CIB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: likely benign (0.1796); Very rare (popmax 8.47e-05%, nfe).

How common is CIB1 p.Ala82Pro (c.244G>C) in the general population?

CIB1 p.Ala82Pro (c.244G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CIB1 p.Ala82Pro (c.244G>C)?

AlphaMissense predicts likely benign (score 0.1796) — an in-silico prediction, not a clinical call.

CIB1 p.Ala82Pro

c.244G>C · rs562237879 · VCV1524552

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1796 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1796	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -10.86	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.72	GERP -2.8
Regional constraint	o/e 0.97	unconstrained · MANE · 3,398 bp · p 0.67 · regional, not allelic
Overall
CADD	5.645	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 8.47e-05% European (non-Finnish) · 1/1,180,040 alleles

Overall 6.84e-05% 1/1,461,874 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: CIB1
Protein: p.Ala82Pro
Coding: c.244G>C
MANE Select: NM_006384
dbSNP: rs562237879
Type: single nucleotide variant
Location: chr15:90231459 (GRCh38)
Gene constraint: LOEUF 1.233 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.37 · 9 PDB
Residue 82: a UniProt-annotated variant site (in ev3; absence of cib1 protein in homozygous patient cells); a β-strand

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

Similar variants

CIB1 p.Ala82Thr Benign ★ same residue
CIB1 p.Ala82fs Pathogenic ★ same residue
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
CIB1 p.Arg143Trp Uncertain significance ★★ ⚠ same type
CIB1 p.Arg72Gln 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-ala82pro (accessed [today's date]).

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