Is CIB1 p.Arg130Trp (c.388C>T) pathogenic?

CIB1 p.Arg130Trp (c.388C>T) is classified Uncertain significance in CIB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-19). AlphaMissense: likely benign (0.1293); Very rare (popmax 0.00834%, amr).

How common is CIB1 p.Arg130Trp (c.388C>T) in the general population?

CIB1 p.Arg130Trp (c.388C>T) is very rare (popmax 0.00834%, amr) (gnomAD).

What do computational predictors say about CIB1 p.Arg130Trp (c.388C>T)?

AlphaMissense predicts likely benign (score 0.1293) — an in-silico prediction, not a clinical call.

CIB1 p.Arg130Trp

c.388C>T · rs775021192 · VCV1427465

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1293 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1293	likely benign
REVEL	0.255	benign-leaning
SaProt	LLR -11.82	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 8.5	GERP 0.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 3,398 bp · p 0.67 · regional, not allelic
Overall
CADD	28.8	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 0.00834% Admixed American · 5/59,964 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00223% 36/1,613,940 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,993
Finnishnot grpmax-eligible	0.00312%	32,007
African / African-American	0.00267%	37,433
European (non-Finnish)	0.0022%	45,386
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Arg130Trp
Coding: c.388C>T
MANE Select: NM_006384
dbSNP: rs775021192
Type: single nucleotide variant
Location: chr15:90231172 (GRCh38)
Gene constraint: LOEUF 1.233 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.37 · 9 PDB
Residue 130: a UniProt-annotated variant site (in ev3; absence of cib1 protein in homozygous patient cells); the ef-hand 1 domain; an α-helix

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

Similar variants

CIB1 p.Arg130= Likely benign ★ same residue
CIB1 p.Arg130Gln Likely benign ★ 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-arg130trp (accessed [today's date]).

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