Is MSX2 p.Pro241Arg (c.722C>G) pathogenic?

MSX2 p.Pro241Arg (c.722C>G) is classified Uncertain significance in MSX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-17). AlphaMissense: ambiguous (0.3672); Absent from gnomAD v4.1.

How common is MSX2 p.Pro241Arg (c.722C>G) in the general population?

MSX2 p.Pro241Arg (c.722C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MSX2 p.Pro241Arg (c.722C>G)?

AlphaMissense predicts ambiguous (score 0.3672) — an in-silico prediction, not a clinical call.

MSX2 p.Pro241Arg

c.722C>G · rs368570722 · VCV2502818

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3672 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3672	ambiguous
REVEL	0.468	indeterminate
SaProt	LLR -8.55	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 409 bp · p 0.00015 · regional, not allelic
Overall
CADD	25.4	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

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: MSX2
Protein: p.Pro241Arg
Coding: c.722C>G
MANE Select: NM_002449
dbSNP: rs368570722
Type: single nucleotide variant
Location: chr5:174729501 (GRCh38)
Gene constraint: LOEUF 1.013 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 68.77

Full MSX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MSX2 p.Pro241Leu Uncertain significance ★★ ⚠ same residue
MSX2 p.Pro241= Benign/Likely benign ★★ same residue
MSX2 p.Pro241Ala Uncertain significance ★ ⚠ same residue
MSX2 p.Gln153Ter Pathogenic/Likely pathogenic ★★ same type
MSX2 p.Pro148His Pathogenic ★★ same type
MSX2 p.Ala212Gly Uncertain significance ★★ ⚠ same type
MSX2 p.Ala232Val Uncertain significance ★★ ⚠ same type
MSX2 p.Ala238Thr 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/msx2-p-pro241arg (accessed [today's date]).

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