Is MESP2 p.Thr69= (c.207G>T) pathogenic?

MESP2 p.Thr69= (c.207G>T) is classified Likely benign in MESP2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-04-13). Very rare (popmax 0.00393%, amr); Associated with spondylocostal dysostosis 2, autosomal recessive.

What condition is associated with MESP2 p.Thr69= (c.207G>T)?

MESP2 p.Thr69= (c.207G>T) is associated with spondylocostal dysostosis 2, autosomal recessive (ClinVar).

How common is MESP2 p.Thr69= (c.207G>T) in the general population?

MESP2 p.Thr69= (c.207G>T) is very rare (popmax 0.00393%, amr) (gnomAD).

MESP2 p.Thr69=

c.207G>T · rs571669966 · VCV1157167

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00393%, amr)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.61	GERP -4.4
Overall
CADD	4.693	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00393% Admixed American · 2/50,848 alleles

Filtering AF 0.00126% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00107%

Overall 0.00176% 27/1,531,716 alleles · very rare exomes 22/1,379,340 · genomes 5/152,376 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00393%	25,424
Remaining individualsnot grpmax-eligible	0.00335%	29,864
European (non-Finnish)	0.00192%	52,043
African / African-American	0.00139%	72,018

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.Thr69=
Coding: c.207G>T
MANE Select: NM_001039958
dbSNP: rs571669966
Type: single nucleotide variant
Location: chr15:89776564 (GRCh38)
Gene constraint: LOEUF 1.656 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.92
Residue 69: 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.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-thr69 (accessed [today's date]).

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