Is MESP2 p.Pro52Ser (c.154C>T) pathogenic?

MESP2 p.Pro52Ser (c.154C>T) is classified Likely benign in MESP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: likely benign (0.0792); Very rare (popmax 0.00413%, afr); Associated with Inborn genetic diseases.

What condition is associated with MESP2 p.Pro52Ser (c.154C>T)?

MESP2 p.Pro52Ser (c.154C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MESP2 p.Pro52Ser (c.154C>T) in the general population?

MESP2 p.Pro52Ser (c.154C>T) is very rare (popmax 0.00413%, afr) (gnomAD).

What do computational predictors say about MESP2 p.Pro52Ser (c.154C>T)?

AlphaMissense predicts likely benign (score 0.0792) — an in-silico prediction, not a clinical call.

MESP2 p.Pro52Ser

c.154C>T · VCV3872314

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0792 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00413%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0792	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -7.01	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 -2.1	GERP -4.3
Regional constraint	o/e 1.18	unconstrained · MANE · 1,973 bp · p 1.6e-05 · regional, not allelic
Overall
CADD	0.229	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

Grpmax group 0.00413% African / African-American · 3/72,578 alleles

Filtering AF 0.0011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000504%

Overall 0.000261% 4/1,533,358 alleles · very rare exomes 2/1,381,140 · genomes 2/152,218 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00413%	24,193
Admixed American	0.00197%	50,864

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.Pro52Ser
Coding: c.154C>T
MANE Select: NM_001039958
Type: single nucleotide variant
Location: chr15:89776511 (GRCh38)
Gene constraint: LOEUF 1.656 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.92
Residue 52: 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-pro52ser (accessed [today's date]).

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