Is MESP2 p.Ala79= (c.237G>T) pathogenic?

MESP2 p.Ala79= (c.237G>T) is classified Likely benign in MESP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-02-17). Ultra-rare (popmax 0.0128%, eas); Associated with spondylocostal dysostosis 2, autosomal recessive.

What condition is associated with MESP2 p.Ala79= (c.237G>T)?

MESP2 p.Ala79= (c.237G>T) is associated with spondylocostal dysostosis 2, autosomal recessive (ClinVar).

How common is MESP2 p.Ala79= (c.237G>T) in the general population?

MESP2 p.Ala79= (c.237G>T) is ultra-rare (popmax 0.0128%, eas) (gnomAD).

MESP2 p.Ala79=

c.237G>T · rs775834437 · VCV794006

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0128%, eas)

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 -8.6	GERP -4.2
Overall
CADD	0.221	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0128% East Asian · 5/39,162 alleles

Filtering AF 0.00496% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0032%

Overall 0.000852% 13/1,526,136 alleles · ultra-rare exomes 11/1,373,876 · genomes 2/152,260 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0128%	7,832
African / African-American	0.00284%	35,264
South Asian	0.00121%	82,774
European (non-Finnish)	0.000437%	228,661

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.Ala79=
Coding: c.237G>T
MANE Select: NM_001039958
dbSNP: rs775834437
Type: single nucleotide variant
Location: chr15:89776594 (GRCh38)
Gene constraint: LOEUF 1.656 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.92
Residue 79: 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.Ala79Thr 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-ala79 (accessed [today's date]).

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