Is MSMO1 p.Trp95Ser (c.284G>C) pathogenic?

MSMO1 p.Trp95Ser (c.284G>C) is classified Uncertain significance in MSMO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: ambiguous (0.5521); Very rare (popmax 0.00667%, amr).

How common is MSMO1 p.Trp95Ser (c.284G>C) in the general population?

MSMO1 p.Trp95Ser (c.284G>C) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about MSMO1 p.Trp95Ser (c.284G>C)?

AlphaMissense predicts ambiguous (score 0.5521) — an in-silico prediction, not a clinical call.

MSMO1 p.Trp95Ser

c.284G>C · rs375770332 · VCV2517183

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5521 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Computational evidence

Protein change
AlphaMissense	0.5521	ambiguous
REVEL	0.517	indeterminate
SaProt	LLR -10.80	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 0.82, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 8,572 bp · p 0.0022 · regional, not allelic
Overall
CADD	26.6	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 0.00667% Admixed American · 4/59,992 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00149% 24/1,613,492 alleles · very rare exomes 22/1,461,352 · genomes 2/152,140 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,998
Remaining individualsnot grpmax-eligible	0.0032%	31,230
European (non-Finnish)	0.00153%	65,542

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.Trp95Ser
Coding: c.284G>C
MANE Select: NM_006745
dbSNP: rs375770332
Type: single nucleotide variant
Location: chr4:165337817 (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-trp95ser (accessed [today's date]).

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