ICMT p.Val188=
c.564G>A · rs35465282 · VCV775494
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 7.51%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.7 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 11.86 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
7.51%
African / African-American · 5,633/74,978 alleles
Filtering AF
7.35%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 7.28%
Overall
0.406%
6,552/1,614,058 alleles · common
exomes 3,291/1,461,848 · genomes 3,261/152,210 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 7.51% | 13 |
| Remaining individualsnot grpmax-eligible | 0.57% | 176 |
| Admixed American | 0.537% | 186 |
| Middle Eastern | 0.347% | 289 |
| Ashkenazi Jewishnot grpmax-eligible | 0.155% | 644 |
| South Asian | 0.0209% | 4,793 |
| European (non-Finnish) | 0.0131% | 7,662 |
| Finnishnot grpmax-eligible | 0.00156% | 64,022 |
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
- ICMT
- Protein
- p.Val188=
- Coding
- c.564G>A
- MANE Select
- NM_012405
- dbSNP
- rs35465282
- Type
- single nucleotide variant
- Location
- chr1:6232010 (GRCh38)
- Gene constraint
- LOEUF 0.604 · pLI 0.74 (gnomAD)
- Structure
- AlphaFold pLDDT 93.57
Similar variants
- ICMT p.Ala176Val Uncertain significance ★ ⚠ same type
- ICMT p.Ala19Ser Uncertain significance ★ ⚠ same type
- ICMT p.Ala2Glu Uncertain significance ★ ⚠ same type
- ICMT p.Ala2Ser Uncertain significance ★ ⚠ same type
- ICMT p.Ala36Thr Uncertain significance ★ ⚠ same type
- ICMT p.Ala6Ser Uncertain significance ★ ⚠ same type
- ICMT p.Arg209Gln Uncertain significance ★ ⚠ same type
- ICMT p.Arg242Gln 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/icmt-p-val188 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown