HAND2 p.Phe119=
c.357C>T · VCV3718652
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.028%, 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 7.3 | GERP -1.4, phastCons 1 |
| Overall | ||
| CADD | 14.63 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.028%
African / African-American · 21/75,026 alleles
Filtering AF
0.0187%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0157%
Overall
0.00167%
27/1,614,028 alleles · ultra-rare
exomes 13/1,461,808 · genomes 14/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.028% | 3,573 |
| Admixed American | 0.00666% | 15,006 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,504 |
| European (non-Finnish) | 8.47e-05% | 1,180,008 |
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.Phe119=
- Coding
- c.357C>T
- MANE Select
- NM_021973
- Type
- single nucleotide variant
- Location
- chr4:173528933 (GRCh38)
- Gene constraint
- LOEUF 0.601 · pLI 0.89 (gnomAD)
- Structure
- AlphaFold pLDDT 67.30
- Residue 119
- 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-phe119 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown