Is SRPRB p.Trp54Arg (c.160T>C) pathogenic?

SRPRB p.Trp54Arg (c.160T>C) is classified Uncertain significance in SRPRB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). AlphaMissense: likely pathogenic (0.8036); Ultra-rare (popmax 0.0827%, afr).

How common is SRPRB p.Trp54Arg (c.160T>C) in the general population?

SRPRB p.Trp54Arg (c.160T>C) is ultra-rare (popmax 0.0827%, afr) (gnomAD).

What do computational predictors say about SRPRB p.Trp54Arg (c.160T>C)?

AlphaMissense predicts likely pathogenic (score 0.8036) — an in-silico prediction, not a clinical call.

SRPRB p.Trp54Arg

c.160T>C · rs147764661 · VCV3170055

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8036 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0827%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8036	likely pathogenic
REVEL	0.219	benign-leaning
SaProt	LLR -8.38	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 14 kb · p 0.83 · regional, not allelic
Overall
CADD	27.9	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 0.0827% African / African-American · 62/74,946 alleles

Filtering AF 0.0661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0602%

Overall 0.00477% 77/1,613,934 alleles · ultra-rare exomes 47/1,461,684 · genomes 30/152,250 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0827%	1,209
Remaining individualsnot grpmax-eligible	0.0128%	7,810
Admixed American	0.0117%	8,573

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.Trp54Arg
Coding: c.160T>C
MANE Select: NM_001379313
dbSNP: rs147764661
Type: single nucleotide variant
Location: chr3:133806614 (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.Arg58Gln 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

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-trp54arg (accessed [today's date]).

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