BHLHE41 p.Arg34=
c.100A>C · rs137958863 · VCV2642801
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.123%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 6.1 | GERP 0.29, phastCons 1 |
| Overall | ||
| CADD | 13.78 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.123%
South Asian · 112/91,078 alleles
Filtering AF
0.104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0975%
Overall
0.0213%
344/1,614,124 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.123% | 813 |
| Remaining individualsnot grpmax-eligible | 0.072% | 1,389 |
| Middle Eastern | 0.066% | 1,515 |
| African / African-American | 0.024% | 4,168 |
| European (non-Finnish) | 0.0133% | 7,516 |
| Finnishnot grpmax-eligible | 0.00937% | 10,669 |
| Admixed American | 0.00333% | 30,010 |
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
- BHLHE41
- Protein
- p.Arg34=
- Coding
- c.100A>C
- MANE Select
- NM_030762
- dbSNP
- rs137958863
- Type
- single nucleotide variant
- Location
- chr12:26124545 (GRCh38)
- Gene constraint
- LOEUF 1.219 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 56.72
Similar variants
- BHLHE41 p.Ala360= Likely benign ★★ same type
- BHLHE41 p.Leu372= Benign/Likely benign ★★ same type
- BHLHE41 p.Ala170Val Uncertain significance ★ ⚠ same type
- BHLHE41 p.Ala228Thr Uncertain significance ★ ⚠ same type
- BHLHE41 p.Ala260Thr Uncertain significance ★ ⚠ same type
- BHLHE41 p.Ala299Val Uncertain significance ★ ⚠ same type
- BHLHE41 p.Ala301Thr Uncertain significance ★ ⚠ same type
- BHLHE41 p.Ala302Asp 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/bhlhe41-p-arg34 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown