Is MBTPS2 p.Pro243Ser (c.727C>T) pathogenic?

MBTPS2 p.Pro243Ser (c.727C>T) is classified Uncertain significance in MBTPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2015-06-24). AlphaMissense: likely pathogenic (0.7713); Absent from gnomAD v4.1.

How common is MBTPS2 p.Pro243Ser (c.727C>T) in the general population?

MBTPS2 p.Pro243Ser (c.727C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MBTPS2 p.Pro243Ser (c.727C>T)?

AlphaMissense predicts likely pathogenic (score 0.7713) — an in-silico prediction, not a clinical call.

MBTPS2 p.Pro243Ser

c.727C>T · rs886042131 · VCV281339

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7713 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7713	likely pathogenic
REVEL	0.793	moderately pathogenic-leaning
SaProt	LLR -11.27	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 43 kb · p 4.2e-13 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MBTPS2
Protein: p.Pro243Ser
Coding: c.727C>T
MANE Select: NM_015884
dbSNP: rs886042131
Type: single nucleotide variant
Location: chrX:21868523 (GRCh38)
Structure: AlphaFold pLDDT 87.78

Full MBTPS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MBTPS2 c.970+5G>A Pathogenic ★★ same type
MBTPS2 p.Arg429His Pathogenic ★★ same type
MBTPS2 p.Asn508Ser Pathogenic ★★ same type
MBTPS2 p.Ala507Val Uncertain significance ★★ same type
MBTPS2 p.Arg327Gln Uncertain significance ★★ ⚠ same type
MBTPS2 p.Arg59His Uncertain significance ★★ ⚠ same type
MBTPS2 p.Asn40Thr Uncertain significance ★★ ⚠ same type
MBTPS2 p.Asp292Gly Uncertain significance ★★ ⚠ same type

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/mbtps2-p-pro243ser (accessed [today's date]).

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