Is MSRB3 p.Ser62Arg (c.184A>C) pathogenic?

MSRB3 p.Ser62Arg (c.184A>C) is classified Uncertain significance in MSRB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-15). AlphaMissense: ambiguous (0.3418); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MSRB3 p.Ser62Arg (c.184A>C)?

MSRB3 p.Ser62Arg (c.184A>C) is associated with Inborn genetic diseases (ClinVar).

How common is MSRB3 p.Ser62Arg (c.184A>C) in the general population?

MSRB3 p.Ser62Arg (c.184A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MSRB3 p.Ser62Arg (c.184A>C)?

AlphaMissense predicts ambiguous (score 0.3418) — an in-silico prediction, not a clinical call.

MSRB3 p.Ser62Arg

c.184A>C · rs2499009020 · VCV2261680

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3418 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3418	ambiguous
REVEL	0.559	indeterminate
SaProt	LLR -3.14	tolerated
Splicing
SpliceAI	Δ0.21	donor gain · deltas
Pangolin	Δ0.54	gain · loss 0.20 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 155 kb · p 0.039 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S69R vs ClinVar S62R) — verify the residue.

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: MSRB3
Protein: p.Ser62Arg
Coding: c.184A>C
MANE Select: NM_001031679
dbSNP: rs2499009020
Type: single nucleotide variant
Location: chr12:65326933 (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 69 UniProt numbering: the msrb domain

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-ser62arg (accessed [today's date]).

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