Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Common
common (popmax 53%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
1
autosomal recessive congenital ichthyosis 10
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 -5.2 | GERP -2.8 |
| Overall | ||
| CADD | 4.966 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
53%
African / African-American · 39,661/74,834 alleles
Filtering AF
52.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 52.4%
Overall
38.3%
618,325/1,612,774 alleles · common
exomes 554,323/1,460,936 · genomes 64,002/151,838 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 53% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 48.4% | 2 |
| Middle Eastern | 41.8% | 2 |
| Remaining individualsnot grpmax-eligible | 39.9% | 3 |
| European (non-Finnish) | 38.2% | 3 |
| Finnishnot grpmax-eligible | 37.6% | 3 |
| South Asian | 33.8% | 3 |
| East Asian | 31.2% | 3 |
| Amishnot grpmax-eligible | 30.1% | 3 |
| Admixed American | 28.7% | 3 |
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
- PNPLA1
- Protein
- p.Phe153=
- Coding
- c.459C>T
- MANE Select
- NM_001374623
- dbSNP
- rs2239795
- Type
- single nucleotide variant
- Location
- chr6:36293081 (GRCh38)
- Gene constraint
- LOEUF 0.945 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.54
- Residue 153
- the pnpla domain; a UniProt-annotated variant site (in arci10; loss of omega-hydroxyceramide transacylase activity)
Disease context
autosomal recessive congenital ichthyosis 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Congenital ichthyosiform erythroderma (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
- Prevalence
- 1-9 / 1 000 000 (Spain)
Similar variants
- PNPLA1 p.Ala34Pro Pathogenic/Likely pathogenic ★★ same condition
- PNPLA1 p.Ala50Glu Pathogenic/Likely pathogenic ★★ same condition
- PNPLA1 p.Arg298Ter Pathogenic/Likely pathogenic ★★ same condition
- PNPLA1 p.Asp129Glu Pathogenic/Likely pathogenic ★★ same condition
- PNPLA1 p.Cys216Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
- PNPLA1 p.Pro155Leu Likely pathogenic ★★ same condition
- PNPLA1 p.Pro163Leu Pathogenic/Likely pathogenic ★★ same condition
- PNPLA1 p.Ser53Leu Likely pathogenic ★★ same condition
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/pnpla1-p-phe153 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown