IHH p.Pro331=
c.993G>A · VCV4959918
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0201%, eas)
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 -4 | GERP -5 |
| Overall | ||
| CADD | 0.467 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0201%
East Asian · 9/44,842 alleles
Filtering AF
0.0104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0078%
Overall
0.00292%
47/1,611,892 alleles · ultra-rare
exomes 41/1,459,532 · genomes 6/152,360 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0201% | 4,982 |
| Admixed American | 0.00333% | 29,996 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,210 |
| African / African-American | 0.00267% | 37,521 |
| European (non-Finnish) | 0.00263% | 38,031 |
| South Asian | 0.0011% | 91,060 |
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
- IHH
- Protein
- p.Pro331=
- Coding
- c.993G>A
- MANE Select
- NM_002181
- Type
- single nucleotide variant
- Location
- chr2:219055450 (GRCh38)
- Gene constraint
- LOEUF 0.544 · pLI 0.94 (gnomAD)
- Structure
- AlphaFold pLDDT 84.84 · 8 PDB
Similar variants
- IHH p.Pro331Leu Uncertain significance ★★ ⚠ same residue
- IHH p.Arg158Cys Pathogenic/Likely pathogenic ★★ same type
- IHH p.Asp100Asn Pathogenic ★★ same type
- IHH p.Met1Val Likely pathogenic ★★ same type
- IHH c.*423G>A Uncertain significance ★★ same type
- IHH p.Ala216Val Uncertain significance ★★ ⚠ same type
- IHH p.Ala270Val Uncertain significance ★★ ⚠ same type
- IHH p.Ala274Thr Uncertain significance ★★ ⚠ 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/ihh-p-pro331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown