Is SRPRB p.Arg58Gln (c.173G>A) pathogenic?

SRPRB p.Arg58Gln (c.173G>A) is classified Uncertain significance in SRPRB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-06). AlphaMissense: likely benign (0.081); Very rare (popmax 0.00267%, afr).

How common is SRPRB p.Arg58Gln (c.173G>A) in the general population?

SRPRB p.Arg58Gln (c.173G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about SRPRB p.Arg58Gln (c.173G>A)?

AlphaMissense predicts likely benign (score 0.081) — an in-silico prediction, not a clinical call.

SRPRB p.Arg58Gln

c.173G>A · rs745490539 · VCV2383062

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.081 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.081	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -7.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 14 kb · p 0.83 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,912 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00204% 33/1,613,908 alleles · very rare exomes 31/1,461,732 · genomes 2/152,176 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,456
European (non-Finnish)	0.00254%	39,331
Remaining individualsnot grpmax-eligible	0.0016%	62,476

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: SRPRB
Protein: p.Arg58Gln
Coding: c.173G>A
MANE Select: NM_001379313
dbSNP: rs745490539
Type: single nucleotide variant
Location: chr3:133806627 (GRCh38)
Gene constraint: LOEUF 1.05 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.30 · 1 PDB

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

Similar variants

SRPRB p.Ala211Val Uncertain significance ★ ⚠ same type
SRPRB p.Arg109Lys Uncertain significance ★ ⚠ same type
SRPRB p.Arg150Gln Uncertain significance ★ ⚠ same type
SRPRB p.Arg208His Uncertain significance ★ ⚠ same type
SRPRB p.Asn106Ser Uncertain significance ★ ⚠ same type
SRPRB p.Asn171Ser Uncertain significance ★ ⚠ same type
SRPRB p.Asn171Thr Uncertain significance ★ ⚠ same type
SRPRB p.Asp259Tyr 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/srprb-p-arg58gln (accessed [today's date]).

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