Is MESP2 p.Val138fs (c.413del) pathogenic?

MESP2 p.Val138fs (c.413del) is classified Pathogenic in MESP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-09). Associated with spondylocostal dysostosis 2, autosomal recessive.

What condition is associated with MESP2 p.Val138fs (c.413del)?

MESP2 p.Val138fs (c.413del) is associated with spondylocostal dysostosis 2, autosomal recessive (ClinVar).

MESP2 p.Val138fs

c.413del · VCV4081733

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

spondylocostal dysostosis 2, autosomal recessive

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 1 of 2
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP -2.2, phastCons 1

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

Variant & gene context

Gene: MESP2
Protein: p.Val138fs
Coding: c.413del
MANE Select: NM_001039958
Type: Deletion
Location: chr15:89776770 (GRCh38)
Gene constraint: LOEUF 1.656 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.92
Residue 138: a UniProt-annotated variant site (in)

Full MESP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spondylocostal dysostosis 2, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MESP2 p.Val138Met Benign ★★ same residue
MESP2 p.Val138Leu Uncertain significance ⚠ same residue
MESP2 p.180_181QG[7] Benign/Likely benign ★★ same condition
MESP2 p.Arg341fs Likely pathogenic ★ same condition
MESP2 p.Gln180fs Likely pathogenic ★ same condition
MESP2 p.Gln182fs Likely pathogenic ★ same condition
MESP2 p.Gln186fs Likely pathogenic ★ same condition
MESP2 p.Gln190fs Likely 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/mesp2-p-val138fs (accessed [today's date]).

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