PHIP p.Cys188=
c.564T>C · rs35686657 · VCV780641
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 7.16%, 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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 11.49 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
7.16%
African / African-American · 5,353/74,752 alleles
Filtering AF
7%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.94%
Overall
0.397%
6,383/1,607,844 alleles · common
exomes 3,162/1,455,608 · genomes 3,221/152,236 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 7.16% | 14 |
| Admixed American | 0.658% | 152 |
| Remaining individualsnot grpmax-eligible | 0.517% | 193 |
| Middle Eastern | 0.315% | 318 |
| European (non-Finnish) | 0.0251% | 3,980 |
| South Asian | 0.0112% | 8,959 |
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
- PHIP
- Protein
- p.Cys188=
- Coding
- c.564T>C
- MANE Select
- NM_017934
- dbSNP
- rs35686657
- Type
- single nucleotide variant
- Location
- chr6:79042879 (GRCh38)
- Gene constraint
- LOEUF 0.246 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.57 · 146 PDB
Similar variants
- PHIP p.Cys188Phe Uncertain significance ★ ⚠ same residue
- PHIP p.Cys188Arg Uncertain significance ★ same residue
- PHIP p.Arg110Cys Pathogenic/Likely pathogenic ★★ same type
- PHIP p.Arg178Ter Pathogenic/Likely pathogenic ★★ same type
- PHIP p.Arg193Ter Pathogenic ★★ same type
- PHIP p.Arg255Ter Pathogenic/Likely pathogenic ★★ same type
- PHIP p.Arg396Ter Pathogenic/Likely pathogenic ★★ same type
- PHIP p.Arg503Ter Pathogenic/Likely pathogenic ★★ 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/phip-p-cys188 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown