Is BSX p.Pro179Leu (c.536C>T) pathogenic?

BSX p.Pro179Leu (c.536C>T) is classified Uncertain significance in BSX (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-30). AlphaMissense: likely benign (0.0755); Ultra-rare (popmax 0.011%, sas).

How common is BSX p.Pro179Leu (c.536C>T) in the general population?

BSX p.Pro179Leu (c.536C>T) is ultra-rare (popmax 0.011%, sas) (gnomAD).

What do computational predictors say about BSX p.Pro179Leu (c.536C>T)?

AlphaMissense predicts likely benign (score 0.0755) — an in-silico prediction, not a clinical call.

BSX p.Pro179Leu

c.536C>T · rs779981498 · VCV2357521

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0755 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0755	likely benign
REVEL	0.342	indeterminate
SaProt	LLR -7.82	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 5.8	GERP 2.1, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 209 bp · p 0.31 · regional, not allelic
Overall
CADD	23.1	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 0.011% South Asian · 10/91,084 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.00663% 107/1,613,868 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0609%	1,641
South Asiangrpmax	0.011%	9,108
Remaining individualsnot grpmax-eligible	0.008%	12,495
European (non-Finnish)	0.00449%	22,263

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro179Leu
Coding: c.536C>T
MANE Select: NM_001098169
dbSNP: rs779981498
Type: single nucleotide variant
Location: chr11:122977815 (GRCh38)
Gene constraint: LOEUF 1.172 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.92
Residue 179: 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-pro179leu (accessed [today's date]).

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