PHIP p.Leu716=
c.2148G>T · rs190382214 · VCV2046810
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.851%, amr)
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 1.7 | GERP -4, phastCons 1 |
| Overall | ||
| CADD | 4.275 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.851%
Admixed American · 511/60,020 alleles
Filtering AF
0.79%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.766%
Overall
0.0828%
1,337/1,613,994 alleles · rare
exomes 1,240/1,461,766 · genomes 97/152,228 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.851% | 117 |
| South Asian | 0.652% | 153 |
| East Asian | 0.348% | 288 |
| Remaining individualsnot grpmax-eligible | 0.0896% | 1,116 |
| Middle Eastern | 0.0825% | 1,212 |
| African / African-American | 0.0147% | 6,818 |
| European (non-Finnish) | 0.000339% | 294,986 |
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.Leu716=
- Coding
- c.2148G>T
- MANE Select
- NM_017934
- dbSNP
- rs190382214
- Type
- single nucleotide variant
- Location
- chr6:78997467 (GRCh38)
- Gene constraint
- LOEUF 0.246 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.57 · 146 PDB
- Residue 716
- a UniProt-annotated variant site (in chujans)
Similar variants
- 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
- PHIP p.Arg721Ter Pathogenic/Likely pathogenic ★★ same type
- PHIP p.Asn507Ser 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-leu716 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown