Is MIP p.Ser126= (c.378C>T) pathogenic?

MIP p.Ser126= (c.378C>T) is classified Benign/Likely benign in MIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-01-22). Rare (popmax 0.642%, eas); Associated with cataract 15 multiple types.

What condition is associated with MIP p.Ser126= (c.378C>T)?

MIP p.Ser126= (c.378C>T) is associated with cataract 15 multiple types (ClinVar).

How common is MIP p.Ser126= (c.378C>T) in the general population?

MIP p.Ser126= (c.378C>T) is rare (popmax 0.642%, eas) (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.Ser126=

c.378C>T · rs35033450 · VCV309885

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.642%, eas)

Conditions

cataract 15 multiple types

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 -1.7	GERP -3.1
Overall
CADD	3.888	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.642% East Asian · 288/44,876 alleles

Filtering AF 0.581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.557%

Overall 0.0254% 410/1,613,746 alleles · rare exomes 383/1,461,418 · genomes 27/152,328 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.642%	156
Ashkenazi Jewishnot grpmax-eligible	0.304%	329
Remaining individualsnot grpmax-eligible	0.0224%	4,464
Admixed American	0.00334%	29,976
African / African-American	0.00133%	75,052
European (non-Finnish)	0.00127%	78,660

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.Ser126=
Coding: c.378C>T
MANE Select: NM_012064
dbSNP: rs35033450
Type: single nucleotide variant
Location: chr12:56453738 (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 c.606+1G>C Pathogenic/Likely pathogenic ★★ same condition
MIP p.Arg33Cys 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
MIP p.Thr108Ile Uncertain significance ★★ ⚠ same condition
MIP p.Val142Met 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-ser126 (accessed [today's date]).

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