Is BARX2 p.Pro271Arg (c.812C>G) pathogenic?

BARX2 p.Pro271Arg (c.812C>G) is classified Uncertain significance in BARX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-25). AlphaMissense: likely benign (0.0813); Very rare (popmax 0.0022%, sas).

How common is BARX2 p.Pro271Arg (c.812C>G) in the general population?

BARX2 p.Pro271Arg (c.812C>G) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about BARX2 p.Pro271Arg (c.812C>G)?

AlphaMissense predicts likely benign (score 0.0813) — an in-silico prediction, not a clinical call.

BARX2 p.Pro271Arg

c.812C>G · rs1448260641 · VCV3133000

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0813 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0813	likely benign
REVEL	0.192	benign-leaning
SaProt	LLR -8.66	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 3.3	GERP -0.11, phastCons 0.43
Regional constraint	o/e 1.04	unconstrained · MANE · 263 bp · p 0.66 · regional, not allelic
Overall
CADD	15.85	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 0.0022% South Asian · 2/91,072 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000137% 2/1,461,664 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: BARX2
Protein: p.Pro271Arg
Coding: c.812C>G
MANE Select: NM_003658
dbSNP: rs1448260641
Type: single nucleotide variant
Location: chr11:129451374 (GRCh38)
Gene constraint: LOEUF 0.729 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 65.88
Residue 271: the 'disordered' region

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-pro271arg (accessed [today's date]).

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