PTF1A p.Ser265=
c.795C>A · VCV4906764
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00134%, 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 -1.3 | GERP -1.7 |
| Overall | ||
| CADD | 7.252 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00134%
African / African-American · 1/74,750 alleles
Filtering AF
0.000431%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000314%
Overall
0.000684%
11/1,607,624 alleles · very rare
exomes 9/1,455,474 · genomes 2/152,150 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00134% | 74,750 |
| European (non-Finnish) | 0.000851% | 117,450 |
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
- PTF1A
- Protein
- p.Ser265=
- Coding
- c.795C>A
- MANE Select
- NM_178161
- Type
- single nucleotide variant
- Location
- chr10:23193714 (GRCh38)
- Gene constraint
- LOEUF 1.878 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.81
- Residue 265
- the 'disordered' region
Similar variants
- PTF1A p.Pro191Thr Pathogenic/Likely pathogenic ★★ same type
- PTF1A p.Ala149Val Uncertain significance ★★ ⚠ same type
- PTF1A p.Ala3Val Uncertain significance ★★ ⚠ same type
- PTF1A p.Arg206Leu Uncertain significance ★★ ⚠ same type
- PTF1A p.Arg63Cys Uncertain significance ★★ ⚠ same type
- PTF1A p.Asp270His Uncertain significance ★★ ⚠ same type
- PTF1A p.Cys121Tyr Uncertain significance ★★ ⚠ same type
- PTF1A p.Gly143Glu Uncertain significance ★★ ⚠ 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/ptf1a-p-ser265 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown