Is MESP2 p.Pro287Ser (c.859C>T) pathogenic?

MESP2 p.Pro287Ser (c.859C>T) is classified Likely benign in MESP2 (ClinVar, Single submitter, 3 submitters; last evaluated 2026-01-20). AlphaMissense: likely benign (0.0965); Rare (popmax 0.233%, afr); Associated with spondylocostal dysostosis 2, autosomal recessive.

What condition is associated with MESP2 p.Pro287Ser (c.859C>T)?

MESP2 p.Pro287Ser (c.859C>T) is associated with spondylocostal dysostosis 2, autosomal recessive (ClinVar).

How common is MESP2 p.Pro287Ser (c.859C>T) in the general population?

MESP2 p.Pro287Ser (c.859C>T) is rare (popmax 0.233%, afr) (gnomAD).

What do computational predictors say about MESP2 p.Pro287Ser (c.859C>T)?

AlphaMissense predicts likely benign (score 0.0965) — an in-silico prediction, not a clinical call.

MESP2 p.Pro287Ser

c.859C>T · rs201904631 · VCV730015

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0965 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.233%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

spondylocostal dysostosis 2, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.0965	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -6.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.077	GERP -3.5, phastCons 0.003
Regional constraint	o/e 1.18	unconstrained · MANE · 1,973 bp · p 1.6e-05 · regional, not allelic
Overall
CADD	13.89	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.233% African / African-American · 175/75,058 alleles

Filtering AF 0.205% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.194%

Overall 0.012% 193/1,612,526 alleles · rare exomes 97/1,460,156 · genomes 96/152,370 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.233%	429
Admixed American	0.0233%	4,284
Remaining individualsnot grpmax-eligible	0.0048%	20,819
European (non-Finnish)	8.48e-05%	1,179,786

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.Pro287Ser
Coding: c.859C>T
MANE Select: NM_001039958
dbSNP: rs201904631
Type: single nucleotide variant
Location: chr15:89777216 (GRCh38)
Gene constraint: LOEUF 1.656 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.92
Residue 287: the 'disordered' region

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.Pro287His Uncertain significance ★ ⚠ same residue
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

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-pro287ser (accessed [today's date]).

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