Is BSX p.Ala66Thr (c.196G>A) pathogenic?

BSX p.Ala66Thr (c.196G>A) is classified Uncertain significance in BSX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-02). AlphaMissense: likely benign (0.0974); Very rare (popmax 0.00189%, nfe).

How common is BSX p.Ala66Thr (c.196G>A) in the general population?

BSX p.Ala66Thr (c.196G>A) is very rare (popmax 0.00189%, nfe) (gnomAD).

What do computational predictors say about BSX p.Ala66Thr (c.196G>A)?

AlphaMissense predicts likely benign (score 0.0974) — an in-silico prediction, not a clinical call.

BSX p.Ala66Thr

c.196G>A · VCV3482700

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0974 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00189%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0974	likely benign
REVEL	0.457	indeterminate
SaProt	LLR -6.61	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 2,380 bp · p 0.41 · regional, not allelic
Overall
CADD	22.0	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

Grpmax group 0.00189% European (non-Finnish) · 22/1,162,236 alleles

Filtering AF 0.00124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00106%

Overall 0.00146% 23/1,579,104 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00189%	52,829
Remaining individualsnot grpmax-eligible	0.00163%	61,276

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.Ala66Thr
Coding: c.196G>A
MANE Select: NM_001098169
Type: single nucleotide variant
Location: chr11:122981476 (GRCh38)
Gene constraint: LOEUF 1.172 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.92

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.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
BSX p.Asp219Gly 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-ala66thr (accessed [today's date]).

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