Is IBA57 p.Pro153= (c.459G>A) pathogenic?

IBA57 p.Pro153= (c.459G>A) is classified Likely benign in IBA57 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-17). Very rare (popmax 6.21e-05%); Associated with multiple mitochondrial dysfunctions syndrome 3.

How common is IBA57 p.Pro153= (c.459G>A) in the general population?

IBA57 p.Pro153= (c.459G>A) is very rare (popmax 6.21e-05%) (gnomAD).

IBA57 p.Pro153=

Q: What condition is associated with IBA57 p.Pro153= (c.459G>A)?

IBA57 p.Pro153= (c.459G>A) is associated with multiple mitochondrial dysfunctions syndrome 3, hereditary spastic paraplegia 74 (ClinVar).

Q: How is Multiple mitochondrial dysfunctions syndrome type 3 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.459G>A · rs2034984342 · VCV2017980

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.21e-05%)

Conditions

multiple mitochondrial dysfunctions syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -8
Overall
CADD	0.309	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.21e-05%

Overall 6.21e-05% 1/1,610,204 alleles · very rare exomes 1/1,457,962 · genomes 0/152,242 · 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: IBA57
Protein: p.Pro153=
Coding: c.459G>A
MANE Select: NM_001010867
dbSNP: rs2034984342
Type: single nucleotide variant
Location: chr1:228174809 (GRCh38)
Gene constraint: LOEUF 1.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.07 · 3 PDB
Residue 153: a β-strand

Full IBA57 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

multiple mitochondrial dysfunctions syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary spastic paraplegia 74

For Multiple mitochondrial dysfunctions syndrome type 3 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

IBA57 p.Arg105Trp Likely pathogenic ★★ same condition
IBA57 p.Gln103Ter Pathogenic ★★ same condition
IBA57 p.Gln116Ter Pathogenic/Likely pathogenic ★★ same condition
IBA57 p.Gln226= Pathogenic ★★ same condition
IBA57 p.Gly104Cys Likely pathogenic ★★ same condition
IBA57 p.Thr106Ala Pathogenic/Likely pathogenic ★★ ⚠ same condition
IBA57 p.Tyr113Ter Pathogenic ★★ same condition
IBA57 p.Tyr96His Pathogenic ★★ 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/iba57-p-pro153 (accessed [today's date]).

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