Is MIB1 p.Pro45= (c.135C>A) pathogenic?

MIB1 p.Pro45= (c.135C>A) is classified Likely benign in MIB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). Very rare (popmax 6.85e-05%); Associated with Inborn genetic diseases.

What condition is associated with MIB1 p.Pro45= (c.135C>A)?

MIB1 p.Pro45= (c.135C>A) is associated with Inborn genetic diseases (ClinVar).

How common is MIB1 p.Pro45= (c.135C>A) in the general population?

MIB1 p.Pro45= (c.135C>A) is very rare (popmax 6.85e-05%) (gnomAD).

MIB1 p.Pro45=

c.135C>A · VCV3395785

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2	GERP -2.7
Overall
CADD	6.333	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.85e-05%

Overall 6.85e-05% 1/1,459,216 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: MIB1
Protein: p.Pro45=
Coding: c.135C>A
MANE Select: NM_020774
Type: single nucleotide variant
Location: chr18:21741718 (GRCh38)
Gene constraint: LOEUF 1.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.09 · 6 PDB
Residue 45: the mib/herc2 1 domain; a β-strand

Full MIB1 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

MIB1 p.Ala148Ser Uncertain significance ★★ ⚠ same condition
MIB1 p.Ala570Val Uncertain significance ★★ ⚠ same condition
MIB1 p.Asn432Ser Uncertain significance ★★ ⚠ same condition
MIB1 p.Asn441Ser Uncertain significance ★★ ⚠ same condition
MIB1 p.Asn656Ser Uncertain significance ★★ ⚠ same condition
MIB1 p.Asn656Thr Uncertain significance ★★ ⚠ same condition
MIB1 p.Cys885Gly Uncertain significance ★★ ⚠ same condition
MIB1 p.Gly802Asp 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/mib1-p-pro45 (accessed [today's date]).

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