Is MESP2 p.Asp29fs (c.86dup) pathogenic?

MESP2 p.Asp29fs (c.86dup) is classified Pathogenic in MESP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-22). Very rare (popmax 8.73e-05%, nfe).

How common is MESP2 p.Asp29fs (c.86dup) in the general population?

MESP2 p.Asp29fs (c.86dup) is very rare (popmax 8.73e-05%, nfe) (gnomAD).

MESP2 p.Asp29fs

c.86dup · rs2505184696 · VCV2848541

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.73e-05%, nfe)

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 6	GERP -1.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.73e-05% European (non-Finnish) · 1/1,146,038 alleles

Overall 6.52e-05% 1/1,534,098 alleles · very rare exomes 1/1,381,744 · genomes 0/152,354 · 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: MESP2
Protein: p.Asp29fs
Coding: c.86dup
MANE Select: NM_001039958
dbSNP: rs2505184696
Type: Duplication
Location: chr15:89776442 (GRCh38)
Gene constraint: LOEUF 1.656 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.92
Residue 29: the 'disordered' region

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

Similar variants

MESP2 p.Cys59fs Pathogenic ★ same type
MESP2 p.Gln188fs Likely pathogenic ★ same type
MESP2 p.Gln55fs Pathogenic ★ same type
MESP2 p.Glu65fs Pathogenic ★ same type
MESP2 p.Gly12fs Pathogenic ★ same type
MESP2 p.Ser142fs Likely pathogenic ★ same type
MESP2 p.Ser158fs Pathogenic ★ same type
MESP2 c.*132_*134dup Uncertain significance ★ same type

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-asp29fs (accessed [today's date]).

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