PHIP p.Ala241=
c.723A>G · rs77379998 · VCV1336136
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.12%, afr)
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 1.9 | GERP -0.84, phastCons 1 |
| Overall | ||
| CADD | 10.85 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.12%
African / African-American · 839/75,048 alleles
Filtering AF
1.06%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.03%
Overall
0.0852%
1,375/1,614,100 alleles · low-frequency
exomes 862/1,461,776 · genomes 513/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.12% | 89 |
| Middle Eastern | 0.313% | 319 |
| Remaining individualsnot grpmax-eligible | 0.158% | 631 |
| Admixed American | 0.158% | 632 |
| Ashkenazi Jewishnot grpmax-eligible | 0.145% | 688 |
| European (non-Finnish) | 0.022% | 4,538 |
| South Asian | 0.022% | 4,554 |
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.Ala241=
- Coding
- c.723A>G
- MANE Select
- NM_017934
- dbSNP
- rs77379998
- Type
- single nucleotide variant
- Location
- chr6:79026042 (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.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-ala241 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown