Is CIB4 p.Arg128Gln (c.383G>A) pathogenic?

CIB4 p.Arg128Gln (c.383G>A) is classified Uncertain significance in CIB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-20). AlphaMissense: likely benign (0.2654); Very rare (popmax 0.00801%, afr).

How common is CIB4 p.Arg128Gln (c.383G>A) in the general population?

CIB4 p.Arg128Gln (c.383G>A) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about CIB4 p.Arg128Gln (c.383G>A)?

AlphaMissense predicts likely benign (score 0.2654) — an in-silico prediction, not a clinical call.

CIB4 p.Arg128Gln

c.383G>A · rs149619875 · VCV3144919

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2654 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2654	likely benign
REVEL	0.391	indeterminate
SaProt	LLR -7.37	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.4, phastCons 0.96
Regional constraint	o/e 1.03	unconstrained · MANE · 60 kb · p 0.65 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,894 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.00285% 46/1,613,382 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,482
East Asian	0.00668%	14,961
European (non-Finnish)	0.00305%	32,772
Remaining individualsnot grpmax-eligible	0.0016%	62,450

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: CIB4
Protein: p.Arg128Gln
Coding: c.383G>A
MANE Select: NM_001029881
dbSNP: rs149619875
Type: single nucleotide variant
Location: chr2:26583844 (GRCh38)
Gene constraint: LOEUF 1.456 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.07
Residue 128: the ef-hand 2 domain

Full CIB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIB4 p.Arg128Leu Uncertain significance ★ ⚠ same residue
CIB4 p.Arg107Cys Uncertain significance ★ ⚠ same type
CIB4 p.Arg179Gln Uncertain significance ★ ⚠ same type
CIB4 p.Arg25Gly Uncertain significance ★ ⚠ same type
CIB4 p.Arg62Gln Uncertain significance ★ ⚠ same type
CIB4 p.Arg69Cys Uncertain significance ★ ⚠ same type
CIB4 p.Asn155Asp Uncertain significance ★ ⚠ same type
CIB4 p.Asp121Asn 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/cib4-p-arg128gln (accessed [today's date]).

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