HAND2 p.Ala131=
c.393C>A · VCV4754603
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 -0.15 | GERP -3.8, phastCons 0.13 |
| Overall | ||
| CADD | 8.837 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,002 alleles
Overall
0.000124%
2/1,614,030 alleles · very rare
exomes 1/1,461,864 · genomes 1/152,166 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,002 |
| 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
- HAND2
- Protein
- p.Ala131=
- Coding
- c.393C>A
- MANE Select
- NM_021973
- Type
- single nucleotide variant
- Location
- chr4:173528897 (GRCh38)
- Gene constraint
- LOEUF 0.601 · pLI 0.89 (gnomAD)
- Structure
- AlphaFold pLDDT 67.30
- Residue 131
- the bhlh domain
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-ala131 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown