Is MSMO1 p.Gln277= (c.831G>A) pathogenic?

MSMO1 p.Gln277= (c.831G>A) is classified Benign in MSMO1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). Common (popmax 7.76%, afr) — too common for a highly-penetrant pathogenic allele.

MSMO1 p.Gln277=

Q: How common is MSMO1 p.Gln277= (c.831G>A) in the general population?

MSMO1 p.Gln277= (c.831G>A) is common (popmax 7.76%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.831G>A · rs17585739 · VCV1229277

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 7.76%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.47	GERP -2.3, phastCons 0.001
Overall
CADD	1.026	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.76% African / African-American · 5,813/74,908 alleles

Filtering AF 7.59% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.53%

Overall 6.03% 97,237/1,612,140 alleles · common exomes 87,787/1,460,032 · genomes 9,450/152,108 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	8.77%	11
African / African-Americangrpmax	7.76%	13
European (non-Finnish)	6.35%	16
Remaining individualsnot grpmax-eligible	5.6%	18
South Asian	5.03%	20
Ashkenazi Jewishnot grpmax-eligible	3.69%	27
Admixed American	2.77%	36
Middle Eastern	1.77%	57
Amishnot grpmax-eligible	0.658%	152
East Asian	0.029%	3,445

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gln277=
Coding: c.831G>A
MANE Select: NM_006745
dbSNP: rs17585739
Type: single nucleotide variant
Location: chr4:165341895 (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-gln277 (accessed [today's date]).

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