Is CIB2 p.Met44Val (c.130A>G) pathogenic?

CIB2 p.Met44Val (c.130A>G) is classified Uncertain significance in CIB2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-15). AlphaMissense: likely benign (0.0917); Very rare (popmax 0.00834%, amr); Associated with Inborn genetic diseases.

What condition is associated with CIB2 p.Met44Val (c.130A>G)?

CIB2 p.Met44Val (c.130A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CIB2 p.Met44Val (c.130A>G) in the general population?

CIB2 p.Met44Val (c.130A>G) is very rare (popmax 0.00834%, amr) (gnomAD).

What do computational predictors say about CIB2 p.Met44Val (c.130A>G)?

AlphaMissense predicts likely benign (score 0.0917) — an in-silico prediction, not a clinical call.

CIB2 p.Met44Val

c.130A>G · rs142260703 · VCV1053652

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0917 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0917	likely benign
REVEL	0.275	benign-leaning
SaProt	LLR -4.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP -2.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 26 kb · p 0.17 · regional, not allelic
Overall
CADD	17.67	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 0.00834% Admixed American · 5/59,988 alleles

Filtering AF 0.00451% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00411%

Overall 0.00452% 73/1,613,980 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,998
European (non-Finnish)	0.00559%	17,879
African / African-American	0.00134%	74,898
South Asian	0.0011%	91,090

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.Met44Val
Coding: c.130A>G
MANE Select: NM_006383
dbSNP: rs142260703
Type: single nucleotide variant
Location: chr15:78111233 (GRCh38)
Gene constraint: LOEUF 1.274 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.71 · 1 PDB
Residue 44: a UniProt-annotated variant site (in dfnb48)

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.Met56Val Uncertain significance ★★ ⚠ same condition
CIB2 p.Met94Val 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-met44val (accessed [today's date]).

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