Is BSPRY p.Cys262Phe (c.785G>T) pathogenic?

BSPRY p.Cys262Phe (c.785G>T) is classified Uncertain significance in BSPRY (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.0837); Absent from gnomAD v4.1.

How common is BSPRY p.Cys262Phe (c.785G>T) in the general population?

BSPRY p.Cys262Phe (c.785G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BSPRY p.Cys262Phe (c.785G>T)?

AlphaMissense predicts likely benign (score 0.0837) — an in-silico prediction, not a clinical call.

BSPRY p.Cys262Phe

c.785G>T · VCV4836919

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0837 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0837	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -3.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.9	GERP 0.14, phastCons 0.88
Regional constraint	o/e 0.98	unconstrained · MANE · 21 kb · p 0.66 · regional, not allelic
Overall
CADD	16.17	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

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: BSPRY
Protein: p.Cys262Phe
Coding: c.785G>T
MANE Select: NM_017688
Type: single nucleotide variant
Location: chr9:113369718 (GRCh38)
Gene constraint: LOEUF 1.216 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.75
Residue 262: the b30.2/spry domain

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-cys262phe (accessed [today's date]).

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