Is BSX p.Asp219Gly (c.656A>G) pathogenic?

BSX p.Asp219Gly (c.656A>G) is classified Uncertain significance in BSX (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-15). AlphaMissense: ambiguous (0.5231); Very rare (popmax 0.000339%, nfe).

How common is BSX p.Asp219Gly (c.656A>G) in the general population?

BSX p.Asp219Gly (c.656A>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about BSX p.Asp219Gly (c.656A>G)?

AlphaMissense predicts ambiguous (score 0.5231) — an in-silico prediction, not a clinical call.

BSX p.Asp219Gly

c.656A>G · rs1864513883 · VCV2249296

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5231 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5231	ambiguous
REVEL	0.598	indeterminate
SaProt	LLR -8.78	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.58	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 209 bp · p 0.31 · regional, not allelic
Overall
CADD	29.6	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 0.000339% European (non-Finnish) · 4/1,179,810 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,460,124 alleles · very rare

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: BSX
Protein: p.Asp219Gly
Coding: c.656A>G
MANE Select: NM_001098169
dbSNP: rs1864513883
Type: single nucleotide variant
Location: chr11:122977695 (GRCh38)
Gene constraint: LOEUF 1.172 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.92
Residue 219: the 'disordered' region

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

Similar variants

BSX p.His231Gln Benign ★★ same type
BSX p.Ser150= Benign ★★ same type
BSX p.Ala66Thr Uncertain significance ★ ⚠ same type
BSX p.Arg133Leu Uncertain significance ★ ⚠ same type
BSX p.Arg190Cys Uncertain significance ★ ⚠ same type
BSX p.Arg48Gln Uncertain significance ★ same type
BSX p.Asp174Asn Uncertain significance ★ ⚠ same type
BSX p.Asp216Tyr 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/bsx-p-asp219gly (accessed [today's date]).

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