Is BSPRY p.Arg127Trp (c.379C>T) pathogenic?

BSPRY p.Arg127Trp (c.379C>T) is classified Uncertain significance in BSPRY (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). AlphaMissense: likely benign (0.1762); Very rare (popmax 0.00557%, sas).

How common is BSPRY p.Arg127Trp (c.379C>T) in the general population?

BSPRY p.Arg127Trp (c.379C>T) is very rare (popmax 0.00557%, sas) (gnomAD).

What do computational predictors say about BSPRY p.Arg127Trp (c.379C>T)?

AlphaMissense predicts likely benign (score 0.1762) — an in-silico prediction, not a clinical call.

BSPRY p.Arg127Trp

c.379C>T · rs773758644 · VCV3135320

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1762 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00557%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1762	likely benign
REVEL	0.295	indeterminate
SaProt	LLR -10.44	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -1.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 21 kb · p 0.66 · regional, not allelic
Overall
CADD	25.1	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 0.00557% South Asian · 5/89,714 alleles

Filtering AF 0.00213% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00138%

Overall 0.00087% 14/1,608,822 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00557%	17,943
African / African-American	0.004%	24,991
East Asian	0.00223%	44,762
Admixed American	0.00169%	59,292
European (non-Finnish)	0.000339%	294,697

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: BSPRY
Protein: p.Arg127Trp
Coding: c.379C>T
MANE Select: NM_017688
dbSNP: rs773758644
Type: single nucleotide variant
Location: chr9:113360585 (GRCh38)
Gene constraint: LOEUF 1.216 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.75

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

Similar variants

BSPRY p.Gly373Ser Uncertain significance ★★ ⚠ same type
BSPRY p.Ala261Pro Uncertain significance ★ ⚠ same type
BSPRY p.Ala287Gly Uncertain significance ★ ⚠ same type
BSPRY p.Ala287Ser Uncertain significance ★ ⚠ same type
BSPRY p.Ala287Val Uncertain significance ★ ⚠ same type
BSPRY p.Ala45Gly Uncertain significance ★ ⚠ same type
BSPRY p.Ala82Val Uncertain significance ★ ⚠ same type
BSPRY p.Arg113Trp 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/bspry-p-arg127trp (accessed [today's date]).

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