Is BARX2 p.Ser84Pro (c.250T>C) pathogenic?

BARX2 p.Ser84Pro (c.250T>C) is classified Uncertain significance in BARX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-10). AlphaMissense: likely benign (0.0727); Absent from gnomAD v4.1.

How common is BARX2 p.Ser84Pro (c.250T>C) in the general population?

BARX2 p.Ser84Pro (c.250T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BARX2 p.Ser84Pro (c.250T>C)?

AlphaMissense predicts likely benign (score 0.0727) — an in-silico prediction, not a clinical call.

BARX2 p.Ser84Pro

c.250T>C · rs2497895548 · VCV3132994

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0727 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0727	likely benign
REVEL	0.243	benign-leaning
SaProt	LLR -5.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 67 kb · p 0.46 · regional, not allelic
Overall
CADD	18.65	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: BARX2
Protein: p.Ser84Pro
Coding: c.250T>C
MANE Select: NM_003658
dbSNP: rs2497895548
Type: single nucleotide variant
Location: chr11:129436813 (GRCh38)
Gene constraint: LOEUF 0.729 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 65.88

Full BARX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BARX2 p.Arg252His Benign ★★ same type
BARX2 p.Arg129Gln Uncertain significance ★ ⚠ same type
BARX2 p.Arg135Trp Uncertain significance ★ ⚠ same type
BARX2 p.Arg184His Uncertain significance ★ ⚠ same type
BARX2 p.Arg19Gly Uncertain significance ★ ⚠ same type
BARX2 p.Arg68Gln Uncertain significance ★ ⚠ same type
BARX2 p.Arg68Trp Uncertain significance ★ ⚠ same type
BARX2 p.Arg8Thr 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/barx2-p-ser84pro (accessed [today's date]).

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