Is MSRB3 p.Ala183= (c.549G>A) pathogenic?

MSRB3 p.Ala183= (c.549G>A) is classified Likely benign in MSRB3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-08). Very rare (popmax 0.00246%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MSRB3 p.Ala183= (c.549G>A)?

MSRB3 p.Ala183= (c.549G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MSRB3 p.Ala183= (c.549G>A) in the general population?

MSRB3 p.Ala183= (c.549G>A) is very rare (popmax 0.00246%, nfe) (gnomAD).

MSRB3 p.Ala183=

c.549G>A · rs371314128 · VCV1198457

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Conditions

Inborn genetic diseases

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 -10	GERP -3.7
Overall
CADD	1.199	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00246% European (non-Finnish) · 29/1,180,034 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00198% 32/1,614,024 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00246%	40,691
Admixed American	0.00167%	59,998
Remaining individualsnot grpmax-eligible	0.0016%	62,482
South Asian	0.0011%	91,086

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: MSRB3
Protein: p.Ala183=
Coding: c.549G>A
MANE Select: NM_001031679
dbSNP: rs371314128
Type: single nucleotide variant
Location: chr12:65463313 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI 0.08 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.73 · 2 PDB
Residue 183: a modified residue (phosphoserine); the 'disordered' region

Full MSRB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MSRB3 c.-118C>A Uncertain significance ★★ ⚠ same condition
MSRB3 c.-118C>G Uncertain significance ★★ ⚠ same condition
MSRB3 c.-130C>T Uncertain significance ★★ ⚠ same condition
MSRB3 p.Ala162Val Uncertain significance ★★ ⚠ same condition
MSRB3 p.Arg144His Uncertain significance ★★ ⚠ same condition
MSRB3 p.Asn107Asp Uncertain significance ★★ ⚠ same condition
MSRB3 p.Asp30Gly Uncertain significance ★★ ⚠ same condition
MSRB3 p.Lys31Glu Uncertain significance ★★ ⚠ same condition

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/msrb3-p-ala183 (accessed [today's date]).

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