Is MSMO1 p.Pro126Ala (c.376C>G) pathogenic?

MSMO1 p.Pro126Ala (c.376C>G) is classified Benign in MSMO1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-11-26). AlphaMissense: ambiguous (0.357); Low-frequency (popmax 1.33%, eas).

How common is MSMO1 p.Pro126Ala (c.376C>G) in the general population?

MSMO1 p.Pro126Ala (c.376C>G) is low-frequency (popmax 1.33%, eas) (gnomAD).

What do computational predictors say about MSMO1 p.Pro126Ala (c.376C>G)?

AlphaMissense predicts ambiguous (score 0.357) — an in-silico prediction, not a clinical call.

MSMO1 p.Pro126Ala

c.376C>G · rs188890480 · VCV728609

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.357 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.33%, eas)

Computational evidence

Protein change
AlphaMissense	0.357	ambiguous
REVEL	0.311	indeterminate
SaProt	LLR -7.58	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 8,572 bp · p 0.0022 · regional, not allelic
Overall
CADD	25.0	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 1.33% East Asian · 595/44,754 alleles

Filtering AF 1.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.21%

Overall 0.0444% 717/1,613,390 alleles · low-frequency exomes 647/1,461,194 · genomes 70/152,196 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.33%	75
Remaining individualsnot grpmax-eligible	0.0368%	2,716
South Asian	0.034%	2,937
Middle Eastern	0.0333%	2,999
European (non-Finnish)	0.00559%	17,874

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: MSMO1
Protein: p.Pro126Ala
Coding: c.376C>G
MANE Select: NM_006745
dbSNP: rs188890480
Type: single nucleotide variant
Location: chr4:165337909 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.13

Full MSMO1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MSMO1 p.Ala60Gly Uncertain significance ★★ ⚠ same type
MSMO1 p.Asn236Ser Uncertain significance ★★ ⚠ same type
MSMO1 p.Gly273Glu Uncertain significance ★★ same type
MSMO1 p.His105Gln Uncertain significance ★★ ⚠ same type
MSMO1 p.Ile56Met Uncertain significance ★★ ⚠ same type
MSMO1 p.Phe137Leu Uncertain significance ★★ ⚠ same type
MSMO1 p.Trp135Cys Uncertain significance ★★ ⚠ same type
MSMO1 p.Trp52Cys 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/msmo1-p-pro126ala (accessed [today's date]).

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