Is MLIP p.Ser815fs (c.2443del) pathogenic?

MLIP p.Ser815fs (c.2443del) is classified Pathogenic in MLIP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-10-18). Very rare (popmax 0.00138%, afr); Associated with myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis.

How common is MLIP p.Ser815fs (c.2443del) in the general population?

MLIP p.Ser815fs (c.2443del) is very rare (popmax 0.00138%, afr) (gnomAD).

MLIP p.Ser815fs

Q: What condition is associated with MLIP p.Ser815fs (c.2443del)?

MLIP p.Ser815fs (c.2443del) is associated with myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis (ClinVar).

c.2443del · rs2481953351 · VCV1801321

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00138%, afr)

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 5.3	GERP 1.4, phastCons 1
Region caveats
Repeat context	tandem	(CTTCTC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00138% African / African-American · 1/72,226 alleles

Overall 6.35e-05% 1/1,574,018 alleles · very rare exomes 1/1,427,040 · genomes 0/146,978 · 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: MLIP
Protein: p.Ser815fs
Coding: c.2443del
MANE Select: NM_001281747
dbSNP: rs2481953351
Type: Deletion
Location: chr6:54160742 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 43.75
Residue 815: 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.Val832fs Likely pathogenic ★ same condition
MLIP p.His580fs Pathogenic same condition
MLIP p.Leu758fs Pathogenic same condition
MLIP p.Phe611fs 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-ser815fs (accessed [today's date]).

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