Is BRS3 p.Arg155Ter (c.463C>T) pathogenic?

BRS3 p.Arg155Ter (c.463C>T) is classified Uncertain significance in BRS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-08). Absent from gnomAD v4.1.

How common is BRS3 p.Arg155Ter (c.463C>T) in the general population?

BRS3 p.Arg155Ter (c.463C>T) is absent from gnomAD v4.1 (gnomAD).

BRS3 p.Arg155Ter

c.463C>T · rs2148517068 · VCV1701675

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 3
Splicing
SpliceAI	Δ0.22	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 1.3	GERP -3, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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: BRS3
Protein: p.Arg155Ter
Coding: c.463C>T
MANE Select: NM_001727
dbSNP: rs2148517068
Type: single nucleotide variant
Location: chrX:136490161 (GRCh38)
Structure: AlphaFold pLDDT 79.70 · 6 PDB
Residue 155: a disulfide bond; an α-helix

Full BRS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRS3 p.Ala319Thr Uncertain significance ★ ⚠ same type
BRS3 p.Asn159Ser Uncertain significance ★ ⚠ same type
BRS3 p.Asn195Ser Uncertain significance ★ ⚠ same type
BRS3 p.Asn40Ser Uncertain significance ★ ⚠ same type
BRS3 p.Asp144Asn Uncertain significance ★ ⚠ same type
BRS3 p.Asp303Val Uncertain significance ★ ⚠ same type
BRS3 p.Asp30Asn Uncertain significance ★ ⚠ same type
BRS3 p.Asp39Asn 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/brs3-p-arg155ter (accessed [today's date]).

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