GNPAT p.Pro657=
c.1971T>C · rs140894633 · VCV2054472
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0225%, nfe)
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 | GERP -1.2, phastCons 0.005 |
| Overall | ||
| CADD | 8.252 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0225%
European (non-Finnish) · 228/1,012,050 alleles
Filtering AF
0.0201%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0191%
Overall
0.0167%
238/1,428,124 alleles · ultra-rare
exomes 222/1,275,892 · genomes 16/152,232 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0225% | 4,439 |
| Remaining individualsnot grpmax-eligible | 0.0107% | 9,333 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00354% | 28,254 |
| African / African-American | 0.00281% | 35,621 |
| Admixed American | 0.00168% | 59,542 |
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
- GNPAT
- Protein
- p.Pro657=
- Coding
- c.1971T>C
- MANE Select
- NM_014236
- dbSNP
- rs140894633
- Type
- single nucleotide variant
- Location
- chr1:231276168 (GRCh38)
- Gene constraint
- LOEUF 0.572 · pLI 0.88 (gnomAD)
- Structure
- AlphaFold pLDDT 88.96
Similar variants
- GNPAT p.Pro657Arg Uncertain significance ★ ⚠ same residue
- GNPAT p.Pro657Thr Uncertain significance ★ ⚠ same residue
- GNPAT c.569-3T>G Pathogenic ★★ same type
- GNPAT p.Arg163Ter Pathogenic ★★ same type
- GNPAT p.Arg211Cys Likely pathogenic ★★ same type
- GNPAT p.Arg211His Pathogenic ★★ same type
- GNPAT p.Arg335Ter Likely pathogenic ★★ same type
- GNPAT p.Trp386Ter 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/gnpat-p-pro657 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown