Is MESP2 p.Gln186= (c.558G>A) pathogenic?

MESP2 p.Gln186= (c.558G>A) is classified Benign in MESP2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2021-06-09). Common (popmax 50.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with spondylocostal dysostosis 2, autosomal recessive.

What condition is associated with MESP2 p.Gln186= (c.558G>A)?

MESP2 p.Gln186= (c.558G>A) is associated with spondylocostal dysostosis 2, autosomal recessive (ClinVar).

MESP2 p.Gln186=

Q: How common is MESP2 p.Gln186= (c.558G>A) in the general population?

MESP2 p.Gln186= (c.558G>A) is common (popmax 50.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.558G>A · rs28546919 · VCV257243

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 50.5%, afr) — too common for a highly-penetrant pathogenic allele

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 0.71	GERP 0.41, phastCons 0.3
Overall
CADD	1.307	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 50.5% African / African-American · 12,125/24,010 alleles

Filtering AF 49.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 49.4%

Overall 24.5% 16,381/66,994 alleles · common exomes 8,831/50,886 · genomes 7,550/16,108 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	50.5%	2
South Asian	42.3%	2
Middle Eastern	40%	2
Remaining individualsnot grpmax-eligible	28.2%	4
Admixed American	27.6%	4
European (non-Finnish)	2.77%	36
Ashkenazi Jewishnot grpmax-eligible	0.761%	131
Finnishnot grpmax-eligible	0.329%	304
East Asian	0.216%	463

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.Gln186=
Coding: c.558G>A
MANE Select: NM_001039958
dbSNP: rs28546919
Type: single nucleotide variant
Location: chr15:89776915 (GRCh38)
Gene constraint: LOEUF 1.656 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.92
Residue 186: the 'disordered' region; the '13 x 2 aa tandem repeats of g-q' 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.Gln186Glu Uncertain significance ★ ⚠ same residue
MESP2 p.Gln186fs Likely pathogenic ★ 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

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-gln186 (accessed [today's date]).

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