Is MIP p.Leu55fs (c.162dup) pathogenic?

MIP p.Leu55fs (c.162dup) is classified Pathogenic in MIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-24). Very rare (popmax 0.00133%, afr); Associated with cataract 15 multiple types.

What condition is associated with MIP p.Leu55fs (c.162dup)?

MIP p.Leu55fs (c.162dup) is associated with cataract 15 multiple types (ClinVar).

How common is MIP p.Leu55fs (c.162dup) in the general population?

MIP p.Leu55fs (c.162dup) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Early onset non-syndromic cataract inherited?

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

MIP p.Leu55fs

c.162dup · VCV4727827

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

cataract 15 multiple types

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.4	GERP -1.8, phastCons 0.99

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,052 alleles

Overall 6.2e-05% 1/1,614,062 alleles · very rare exomes 1/1,461,746 · genomes 0/152,316 · 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: MIP
Protein: p.Leu55fs
Coding: c.162dup
MANE Select: NM_012064
Type: Duplication
Location: chr12:56454451 (GRCh38)
Structure: AlphaFold pLDDT 78.91

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

Disease context

cataract 15 multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Early onset non-syndromic cataract (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

MIP p.Leu170fs Pathogenic same condition
MIP c.606+1G>C Pathogenic/Likely pathogenic ★★ same condition
MIP p.Arg33Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
MIP p.Gly213fs Pathogenic/Likely pathogenic ★★ same condition
MIP p.Trp205Ter Pathogenic ★★ same condition
MIP p.Glu232Gln Uncertain significance ★★ ⚠ same condition
MIP p.Gly165Ser Uncertain significance ★★ ⚠ same condition
MIP p.Lys238Thr 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/mip-p-leu55fs (accessed [today's date]).

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