Is CIB1 p.Ala184Pro (c.550G>C) pathogenic?

CIB1 p.Ala184Pro (c.550G>C) is classified Uncertain significance in CIB1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-02). AlphaMissense: ambiguous (0.3512); Ultra-rare (popmax 0.02%, afr).

How common is CIB1 p.Ala184Pro (c.550G>C) in the general population?

CIB1 p.Ala184Pro (c.550G>C) is ultra-rare (popmax 0.02%, afr) (gnomAD).

What do computational predictors say about CIB1 p.Ala184Pro (c.550G>C)?

AlphaMissense predicts ambiguous (score 0.3512) — an in-silico prediction, not a clinical call.

CIB1 p.Ala184Pro

c.550G>C · rs957577705 · VCV1468542

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3512 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3512	ambiguous
REVEL	0.166	moderately benign-leaning
SaProt	LLR -8.83	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 5.8	GERP 1.2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 3,398 bp · p 0.67 · regional, not allelic
Overall
CADD	26.8	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 0.02% African / African-American · 15/74,928 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00989%

Overall 0.000929% 15/1,613,778 alleles · ultra-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.Ala184Pro
Coding: c.550G>C
MANE Select: NM_006384
dbSNP: rs957577705
Type: single nucleotide variant
Location: chr15:90230938 (GRCh38)
Gene constraint: LOEUF 1.233 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.37 · 9 PDB
Residue 184: 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

Similar variants

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
CIB1 p.Asn155Asp Uncertain significance ★★ ⚠ same type
CIB1 p.Asn169Ser Uncertain significance ★★ ⚠ same type
CIB1 p.Asn67Ser 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-ala184pro (accessed [today's date]).

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