IHH p.Pro8=
c.24C>T · rs2469520045 · VCV2852595
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.65e-05%, nfe)
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 4.9 | GERP 0.012, phastCons 1 |
| Overall | ||
| CADD | 13.35 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.65e-05%
European (non-Finnish) · 1/1,156,242 alleles
Overall
6.42e-05%
1/1,557,762 alleles · very rare
exomes 1/1,405,464 · genomes 0/152,298 · joint denominator
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.Pro8=
- Coding
- c.24C>T
- MANE Select
- NM_002181
- dbSNP
- rs2469520045
- Type
- single nucleotide variant
- Location
- chr2:219060444 (GRCh38)
- Gene constraint
- LOEUF 0.544 · pLI 0.94 (gnomAD)
- Structure
- AlphaFold pLDDT 84.84 · 8 PDB
Similar variants
- 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
- IHH p.Ala288Ser 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-pro8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown