Is MESP2 p.Pro339= (c.1017C>T) pathogenic?

MESP2 p.Pro339= (c.1017C>T) is classified Likely benign in MESP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-25). Ultra-rare (popmax 0.0496%, mid); Associated with spondylocostal dysostosis 2, autosomal recessive.

What condition is associated with MESP2 p.Pro339= (c.1017C>T)?

MESP2 p.Pro339= (c.1017C>T) is associated with spondylocostal dysostosis 2, autosomal recessive (ClinVar).

How common is MESP2 p.Pro339= (c.1017C>T) in the general population?

MESP2 p.Pro339= (c.1017C>T) is ultra-rare (popmax 0.0496%, mid) (gnomAD).

MESP2 p.Pro339=

c.1017C>T · rs370227491 · VCV731636

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0496%, mid)

Conditions

spondylocostal dysostosis 2, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.7	GERP -4.5
Overall
CADD	7.165	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0496% Middle Eastern · 3/6,052 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00911% 147/1,613,774 alleles · ultra-rare exomes 114/1,461,480 · genomes 33/152,294 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0496%	2,017
South Asian	0.0439%	2,277
African / African-American	0.0386%	2,588
Admixed American	0.0333%	3,001
Remaining individualsnot grpmax-eligible	0.0208%	4,808
European (non-Finnish)	0.00356%	28,096

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.Pro339=
Coding: c.1017C>T
MANE Select: NM_001039958
dbSNP: rs370227491
Type: single nucleotide variant
Location: chr15:89778157 (GRCh38)
Gene constraint: LOEUF 1.656 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.92

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.Gly77Ter Pathogenic/Likely pathogenic ★★ same condition
MESP2 p.Gly81Ter Pathogenic/Likely pathogenic ★★ same condition
MESP2 p.Ser39Ter Pathogenic/Likely pathogenic ★★ same condition
MESP2 p.Ser42Ter Pathogenic/Likely pathogenic ★★ same condition
MESP2 p.Ser4Ter Pathogenic/Likely pathogenic ★★ same condition
MESP2 c.*107T>C Uncertain significance ★★ same condition
MESP2 p.Ala74Thr Uncertain significance ★★ ⚠ same condition
MESP2 p.Arg73Leu 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/mesp2-p-pro339 (accessed [today's date]).

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