Is MESP2 p.Pro290Ser (c.868C>T) pathogenic?

MESP2 p.Pro290Ser (c.868C>T) is classified Uncertain significance in MESP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely benign (0.0819); Ultra-rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with MESP2 p.Pro290Ser (c.868C>T)?

MESP2 p.Pro290Ser (c.868C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MESP2 p.Pro290Ser (c.868C>T) in the general population?

MESP2 p.Pro290Ser (c.868C>T) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about MESP2 p.Pro290Ser (c.868C>T)?

AlphaMissense predicts likely benign (score 0.0819) — an in-silico prediction, not a clinical call.

MESP2 p.Pro290Ser

c.868C>T · rs1248098686 · VCV2411127

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0819 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0819	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -6.09	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 -0.42	GERP -0.046
Regional constraint	o/e 1.18	unconstrained · MANE · 1,973 bp · p 1.6e-05 · regional, not allelic
Overall
CADD	2.093	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,950 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000682% 11/1,612,168 alleles · ultra-rare exomes 8/1,459,908 · genomes 3/152,260 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,992
African / African-American	0.00133%	74,938
European (non-Finnish)	0.000339%	294,903

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.Pro290Ser
Coding: c.868C>T
MANE Select: NM_001039958
dbSNP: rs1248098686
Type: single nucleotide variant
Location: chr15:89777225 (GRCh38)
Gene constraint: LOEUF 1.656 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.92
Residue 290: the 'disordered' region

Full MESP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MESP2 p.Ser4Ter Pathogenic/Likely pathogenic ★★ same condition
MESP2 p.Ala360Thr Uncertain significance ★★ ⚠ same condition
MESP2 p.Arg288Trp Uncertain significance ★★ ⚠ same condition
MESP2 p.Arg392Cys Uncertain significance ★★ ⚠ same condition
MESP2 p.Arg49Cys Uncertain significance ★★ ⚠ same condition
MESP2 p.Arg73Leu Uncertain significance ★★ ⚠ same condition
MESP2 p.Gln263Glu Uncertain significance ★★ ⚠ same condition
MESP2 p.Gln385Lys 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-pro290ser (accessed [today's date]).

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