HAND2 p.Pro97=
c.291G>A · rs147931838 · VCV1599353
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.129%, afr)
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 -0.19 | GERP -2.3, phastCons 0.018 |
| Overall | ||
| CADD | 11.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.129%
African / African-American · 96/74,622 alleles
Filtering AF
0.108%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.1%
Overall
0.00652%
105/1,609,386 alleles · rare
exomes 42/1,457,634 · genomes 63/151,752 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.129% | 777 |
| Remaining individualsnot grpmax-eligible | 0.00804% | 12,442 |
| Admixed American | 0.00335% | 29,865 |
| East Asian | 0.00224% | 44,618 |
| European (non-Finnish) | 8.49e-05% | 1,178,066 |
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.Pro97=
- Coding
- c.291G>A
- MANE Select
- NM_021973
- dbSNP
- rs147931838
- Type
- single nucleotide variant
- Location
- chr4:173528999 (GRCh38)
- Gene constraint
- LOEUF 0.601 · pLI 0.89 (gnomAD)
- Structure
- AlphaFold pLDDT 67.30
- Residue 97
- the 'disordered' region
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-pro97 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown