PPFIA3 p.Pro657=
c.1971C>T · VCV4281014
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.638%, afr)
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 -0.74 | phastCons 0.007 |
| Overall | ||
| CADD | 7.597 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.638%
African / African-American · 479/75,036 alleles
Filtering AF
0.591%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.572%
Overall
0.0356%
574/1,612,982 alleles · rare
exomes 338/1,460,668 · genomes 236/152,314 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.638% | 157 |
| Remaining individualsnot grpmax-eligible | 0.0497% | 2,013 |
| Admixed American | 0.0434% | 2,306 |
| South Asian | 0.00549% | 18,202 |
| European (non-Finnish) | 0.00271% | 36,864 |
| East Asian | 0.00223% | 44,860 |
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
- PPFIA3
- Protein
- p.Pro657=
- Coding
- c.1971C>T
- MANE Select
- NM_003660
- Type
- single nucleotide variant
- Location
- chr19:49138322 (GRCh38)
- Gene constraint
- LOEUF 0.264 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 70.27
- Residue 657
- the 'disordered' region
Similar variants
- PPFIA3 p.Pro657His Uncertain significance ★ ⚠ same residue
- PPFIA3 p.Arg415Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- PPFIA3 p.Arg778Ter Pathogenic ★★ same type
- PPFIA3 p.Ser906Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
- PPFIA3 p.Arg830Cys Uncertain significance ★★ ⚠ same type
- PPFIA3 p.Pro802Leu Uncertain significance ★★ ⚠ same type
- PPFIA3 p.Ala563Ser Benign ★★ same type
- PPFIA3 c.241-1G>A 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/ppfia3-p-pro657 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown