HAND2 p.Pro51=
c.153C>G · rs59621536 · VCV1263762
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 19%, afr) — too common for a highly-penetrant pathogenic allele
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 0.13 | GERP -1.7, phastCons 0.89 |
| Overall | ||
| CADD | 11.89 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
19%
African / African-American · 12,792/67,312 alleles
Filtering AF
18.7%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 18.6%
Overall
2.38%
35,263/1,479,684 alleles · common
exomes 24,595/1,328,064 · genomes 10,668/151,620 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 19% | 5 |
| East Asian | 18.3% | 5 |
| South Asian | 9.6% | 10 |
| Ashkenazi Jewishnot grpmax-eligible | 5.03% | 20 |
| Remaining individualsnot grpmax-eligible | 4.04% | 25 |
| Middle Eastern | 2.86% | 35 |
| Finnishnot grpmax-eligible | 2.62% | 38 |
| Admixed American | 2.24% | 45 |
| Amishnot grpmax-eligible | 0.549% | 182 |
| European (non-Finnish) | 0.254% | 393 |
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.Pro51=
- Coding
- c.153C>G
- MANE Select
- NM_021973
- dbSNP
- rs59621536
- Type
- single nucleotide variant
- Location
- chr4:173529137 (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-pro51 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown