Is BARHL2 p.Pro97Arg (c.290C>G) pathogenic?

BARHL2 p.Pro97Arg (c.290C>G) is classified Uncertain significance in BARHL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.1085); Absent from gnomAD v4.1.

How common is BARHL2 p.Pro97Arg (c.290C>G) in the general population?

BARHL2 p.Pro97Arg (c.290C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BARHL2 p.Pro97Arg (c.290C>G)?

AlphaMissense predicts likely benign (score 0.1085) — an in-silico prediction, not a clinical call.

BARHL2 p.Pro97Arg

c.290C>G · VCV4645195

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1085 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1085	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -14.65	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 0.33, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,441 bp · p 0.26 · regional, not allelic
Overall
CADD	13.75	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

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: BARHL2
Protein: p.Pro97Arg
Coding: c.290C>G
MANE Select: NM_020063
Type: single nucleotide variant
Location: chr1:90716906 (GRCh38)
Gene constraint: LOEUF 0.629 · pLI 0.62 (gnomAD)
Structure: AlphaFold pLDDT 62.10 · 11 PDB
Residue 97: the 'disordered' region

Full BARHL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BARHL2 p.Ala131Ser Uncertain significance ★ ⚠ same type
BARHL2 p.Ala332Val Uncertain significance ★ ⚠ same type
BARHL2 p.Ala334Thr Uncertain significance ★ ⚠ same type
BARHL2 p.Ala47Val Uncertain significance ★ ⚠ same type
BARHL2 p.Ala99Val Uncertain significance ★ ⚠ same type
BARHL2 p.Arg216Gln Uncertain significance ★ ⚠ same type
BARHL2 p.Arg216Trp Uncertain significance ★ ⚠ same type
BARHL2 p.Arg354Trp 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/barhl2-p-pro97arg (accessed [today's date]).

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