Is MIPEP p.Arg264Ter (c.790C>T) pathogenic?

MIPEP p.Arg264Ter (c.790C>T) is classified Conflicting classifications of pathogenicity in MIPEP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-04-02). Very rare (popmax 0.0034%, sas); Associated with lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome.

How common is MIPEP p.Arg264Ter (c.790C>T) in the general population?

MIPEP p.Arg264Ter (c.790C>T) is very rare (popmax 0.0034%, sas) (gnomAD).

MIPEP p.Arg264Ter

Q: What condition is associated with MIPEP p.Arg264Ter (c.790C>T)?

MIPEP p.Arg264Ter (c.790C>T) is associated with lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome (ClinVar).

Q: How is Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome inherited?

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

c.790C>T · VCV3779851

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0034%, sas)

Conditions

lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 19
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 5, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0034% South Asian · 3/88,168 alleles

Filtering AF 0.000904% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000451%

Overall 0.000207% 3/1,448,218 alleles · very rare

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: MIPEP
Protein: p.Arg264Ter
Coding: c.790C>T
MANE Select: NM_005932
Type: single nucleotide variant
Location: chr13:23869445 (GRCh38)
Gene constraint: LOEUF 1.181 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.33

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

Disease context

lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

MIPEP p.Arg264Gln Uncertain significance ★ ⚠ same residue
MIPEP c.1848+2T>G Likely pathogenic ★★ same condition
MIPEP p.Asp120Asn Likely pathogenic ★★ same condition
MIPEP p.Ala570Thr Uncertain significance ★★ same condition
MIPEP p.Arg202Cys Uncertain significance ★★ same condition
MIPEP p.Arg509His Uncertain significance ★★ ⚠ same condition
MIPEP p.Arg560His Uncertain significance ★★ ⚠ same condition
MIPEP p.Asp168Ala 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/mipep-p-arg264ter (accessed [today's date]).

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