Is MESP2 p.Ser224Pro (c.670T>C) pathogenic?

MESP2 p.Ser224Pro (c.670T>C) is classified Benign in MESP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2010-08-05). AlphaMissense: likely benign (0.0487); Absent from gnomAD v4.1; Associated with spondylocostal dysostosis 2, autosomal recessive.

What condition is associated with MESP2 p.Ser224Pro (c.670T>C)?

MESP2 p.Ser224Pro (c.670T>C) is associated with spondylocostal dysostosis 2, autosomal recessive (ClinVar).

How common is MESP2 p.Ser224Pro (c.670T>C) in the general population?

MESP2 p.Ser224Pro (c.670T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MESP2 p.Ser224Pro (c.670T>C)?

AlphaMissense predicts likely benign (score 0.0487) — an in-silico prediction, not a clinical call.

MESP2 p.Ser224Pro

c.670T>C · rs118204033 · VCV38911

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0487 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

spondylocostal dysostosis 2, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.0487	likely benign
REVEL	0.129	moderately benign-leaning
SaProt	LLR -5.51	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 -0.86	GERP -4.5
Regional constraint	o/e 1.18	unconstrained · MANE · 1,973 bp · p 1.6e-05 · regional, not allelic
Overall
CADD	0.072	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MESP2
Protein: p.Ser224Pro
Coding: c.670T>C
MANE Select: NM_001039958
dbSNP: rs118204033
Type: single nucleotide variant
Location: chr15:89777027 (GRCh38)
Gene constraint: LOEUF 1.656 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.92
Residue 224: the 'disordered' region; 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.Ser224Phe Benign ★★ same residue
MESP2 p.Ser224Tyr Uncertain significance ★ ⚠ same residue
MESP2 p.Ser224= Likely benign ★ 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

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-ser224pro (accessed [today's date]).

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