MACROD2 p.Leu161=
c.483T>G · rs2076945732 · VCV3039790
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00666%, afr)
Conditions
1
MACROD2-related disorder
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 0.33 | GERP -1.5, phastCons 1 |
| Overall | ||
| CADD | 7.824 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00666%
African / African-American · 5/75,056 alleles
Filtering AF
0.00255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00161%
Overall
0.000372%
6/1,613,808 alleles · very rare
exomes 6/1,461,454 · genomes 0/152,354 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00666% | 15,011 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
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
- MACROD2
- Protein
- p.Leu161=
- Coding
- c.483T>G
- MANE Select
- NM_001351661
- dbSNP
- rs2076945732
- Type
- single nucleotide variant
- Location
- chr20:15230004 (GRCh38)
- Gene constraint
- LOEUF 0.724 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.87 · 4 PDB
- Residue 161
- the macro domain; an α-helix
Disease context
MACROD2-related disorder
Similar variants
- MACROD2 c.1232-10C>T Likely benign same condition
- MACROD2 c.1300+5G>T Benign same condition
- MACROD2 p.Leu432Gln Benign same condition
- MACROD2 p.Thr335Met Benign same condition
- MACROD2 p.Thr58Ile Benign same condition
- MACROD2 c.1232-10del Likely benign same condition
- FLRT3 p.Ser30= Likely benign ★★ same type
- FLRT3 p.Thr419= Benign ★★ 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/macrod2-p-leu161 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown