HAND2 p.Asp153=
c.459C>T · rs545495563 · VCV1990379
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.134%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4.9 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 18.46 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.134%
East Asian · 60/44,880 alleles
Filtering AF
0.107%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0968%
Overall
0.00427%
69/1,614,214 alleles · rare
exomes 60/1,461,890 · genomes 9/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.134% | 748 |
| South Asian | 0.00549% | 18,218 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,256 |
| Admixed American | 0.00167% | 60,030 |
| European (non-Finnish) | 8.47e-05% | 1,180,034 |
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
- HAND2
- Protein
- p.Asp153=
- Coding
- c.459C>T
- MANE Select
- NM_021973
- dbSNP
- rs545495563
- Type
- single nucleotide variant
- Location
- chr4:173528831 (GRCh38)
- Gene constraint
- LOEUF 0.601 · pLI 0.89 (gnomAD)
- Structure
- AlphaFold pLDDT 67.30
Similar variants
- HAND2 p.Glu38Gln Uncertain significance ★★ same type
- HAND2 p.Gly162Ser Uncertain significance ★★ ⚠ same type
- HAND2 p.Gly74Ser Uncertain significance ★★ ⚠ same type
- HAND2 p.Lys216Asn Uncertain significance ★★ ⚠ same type
- HAND2 c.556-18C>G Benign/Likely benign ★★ same type
- HAND2 p.Ala164= Likely benign ★★ same type
- HAND2 p.Ala21Thr Likely benign ★★ same type
- HAND2 p.Ala25= Likely 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/hand2-p-asp153 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown