Is MLIP p.Val832fs (c.2494_2497del) pathogenic?

MLIP p.Val832fs (c.24942497del) is classified Likely pathogenic in MLIP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-08). Ultra-rare (popmax 0.0268%, amr); Associated with myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis.

How common is MLIP p.Val832fs (c.2494_2497del) in the general population?

MLIP p.Val832fs (c.2494_2497del) is ultra-rare (popmax 0.0268%, amr) (gnomAD).

MLIP p.Val832fs

Q: What condition is associated with MLIP p.Val832fs (c.2494_2497del)?

MLIP p.Val832fs (c.2494_2497del) is associated with myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis (ClinVar).

c.2494_2497del · VCV3779874

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0268%, amr)

Conditions

myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.1	GERP -2.5, phastCons 1
Overall
CADD	34.0	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 0.0268% Admixed American · 16/59,720 alleles

Filtering AF 0.0237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0228%

Overall 0.0209% 336/1,605,790 alleles · ultra-rare exomes 299/1,453,998 · genomes 37/151,792 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0268%	3,732
European (non-Finnish)	0.0262%	3,822
Remaining individualsnot grpmax-eligible	0.00643%	15,542
African / African-American	0.00536%	18,651
South Asian	0.0033%	30,273
East Asian	0.00224%	44,700
Finnishnot grpmax-eligible	0.00157%	63,896

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: MLIP
Protein: p.Val832fs
Coding: c.2494_2497del
MANE Select: NM_001281747
Type: Deletion
Location: chr6:54160792 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 43.75
Residue 832: the 'disordered' region; a UniProt-annotated variant site (in mmckr1; decreased transcript level in muscle from homozygous patient, no effect on subcellular location); a UniProt-annotated variant site (in mmckr1); a UniProt-annotated variant site (in mmckr1; may decrease the expression level in muscle from homozygous patient); the 'required for interaction with isl1' region

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

Disease context

myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MLIP p.Glu635fs Likely pathogenic ★ same condition
MLIP p.Gly405_Val406insTer Likely pathogenic ★ same condition
MLIP p.His580fs Pathogenic same condition
MLIP p.Leu758fs Pathogenic same condition
MLIP p.Phe611fs Pathogenic same condition
MLIP p.Ser815fs Pathogenic same condition
MLIP p.Arg844Ter Pathogenic ★ same condition
MLIP p.Lys609Ter 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/mlip-p-val832fs (accessed [today's date]).

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