Is MIB1 p.Arg40= (c.118C>A) pathogenic?

MIB1 p.Arg40= (c.118C>A) is classified Likely benign in MIB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-13). Very rare (popmax 0.000424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MIB1 p.Arg40= (c.118C>A)?

MIB1 p.Arg40= (c.118C>A) is associated with Inborn genetic diseases (ClinVar).

How common is MIB1 p.Arg40= (c.118C>A) in the general population?

MIB1 p.Arg40= (c.118C>A) is very rare (popmax 0.000424%, nfe) (gnomAD).

MIB1 p.Arg40=

c.118C>A · rs752663025 · VCV1744471

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

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 4.6	GERP -0.44, phastCons 1
Overall
CADD	13.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,364 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,611,510 alleles · very rare exomes 5/1,459,176 · genomes 0/152,334 · joint denominator

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.Arg40=
Coding: c.118C>A
MANE Select: NM_020774
dbSNP: rs752663025
Type: single nucleotide variant
Location: chr18:21741701 (GRCh38)
Gene constraint: LOEUF 1.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.09 · 6 PDB
Residue 40: 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-arg40 (accessed [today's date]).

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