Is MIP p.Val164Ile (c.490G>A) pathogenic?

MIP p.Val164Ile (c.490G>A) is classified Likely benign in MIP (ClinVar, Single submitter, 2 submitters; last evaluated 2018-01-13). AlphaMissense: likely benign (0.1036); Ultra-rare (popmax 0.0285%, nfe); Associated with cataract 15 multiple types.

What condition is associated with MIP p.Val164Ile (c.490G>A)?

MIP p.Val164Ile (c.490G>A) is associated with cataract 15 multiple types (ClinVar).

How common is MIP p.Val164Ile (c.490G>A) in the general population?

MIP p.Val164Ile (c.490G>A) is ultra-rare (popmax 0.0285%, nfe) (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.

What do computational predictors say about MIP p.Val164Ile (c.490G>A)?

AlphaMissense predicts likely benign (score 0.1036) — an in-silico prediction, not a clinical call.

MIP p.Val164Ile

c.490G>A · rs149279854 · VCV883924

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1036 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0285%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cataract 15 multiple types

Computational evidence

Protein change
AlphaMissense	0.1036	likely benign
REVEL	0.153	moderately benign-leaning
SaProt	LLR -7.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.17	GERP -3.7, phastCons 0.005
Overall
CADD	13.94	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0285% European (non-Finnish) · 336/1,180,060 alleles

Filtering AF 0.0259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.025%

Overall 0.0216% 348/1,614,136 alleles · ultra-rare exomes 332/1,461,882 · genomes 16/152,254 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0285%	3,512
African / African-American	0.00801%	12,491
Remaining individualsnot grpmax-eligible	0.008%	12,498
South Asian	0.0011%	91,096

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.Val164Ile
Coding: c.490G>A
MANE Select: NM_012064
dbSNP: rs149279854
Type: single nucleotide variant
Location: chr12:56453626 (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-val164ile (accessed [today's date]).

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