Is MIB1 p.Ser331= (c.993G>A) pathogenic?

MIB1 p.Ser331= (c.993G>A) is classified Likely benign in MIB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-09). Ultra-rare (popmax 0.0846%, sas); Associated with Inborn genetic diseases.

What condition is associated with MIB1 p.Ser331= (c.993G>A)?

MIB1 p.Ser331= (c.993G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MIB1 p.Ser331= (c.993G>A) in the general population?

MIB1 p.Ser331= (c.993G>A) is ultra-rare (popmax 0.0846%, sas) (gnomAD).

MIB1 p.Ser331=

c.993G>A · rs143937436 · VCV1768672

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0846%, sas)

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 -1.4	GERP -3.7
Overall
CADD	0.984	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0846% South Asian · 77/91,056 alleles

Filtering AF 0.0693% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0637%

Overall 0.00576% 93/1,613,928 alleles · ultra-rare exomes 91/1,461,768 · genomes 2/152,160 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0846%	1,183
Remaining individualsnot grpmax-eligible	0.0048%	20,827
East Asian	0.00223%	44,880
European (non-Finnish)	0.00102%	98,332

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.Ser331=
Coding: c.993G>A
MANE Select: NM_020774
dbSNP: rs143937436
Type: single nucleotide variant
Location: chr18:21791458 (GRCh38)
Gene constraint: LOEUF 1.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.09 · 6 PDB

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.Ser331Leu Uncertain significance ★ ⚠ same residue
MIB1 p.Ser331Ter Uncertain significance same residue
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

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-ser331 (accessed [today's date]).

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