PDCD1 p.Ala268=
c.804T>C · rs2227981 · VCV1226460
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 74.5%, sas) — too common for a highly-penetrant pathogenic allele
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 -5.8 | GERP -2.7 |
| Overall | ||
| CADD | 0.09 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
74.5%
South Asian · 67,838/91,064 alleles
Filtering AF
74%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 73.8%
Overall
60%
968,333/1,612,824 alleles · common
exomes 875,807/1,460,706 · genomes 92,526/152,118 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 74.5% | 1 |
| Amishnot grpmax-eligible | 71.9% | 1 |
| Finnishnot grpmax-eligible | 70.5% | 1 |
| East Asian | 70.4% | 1 |
| Middle Eastern | 63.2% | 2 |
| Admixed American | 62.8% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 62.2% | 2 |
| Remaining individualsnot grpmax-eligible | 61% | 2 |
| European (non-Finnish) | 57.8% | 2 |
| African / African-American | 57.8% | 2 |
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
- PDCD1
- Protein
- p.Ala268=
- Coding
- c.804T>C
- MANE Select
- NM_005018
- dbSNP
- rs2227981
- Type
- single nucleotide variant
- Location
- chr2:241851121 (GRCh38)
- Gene constraint
- LOEUF 0.891 · pLI 0.03 (gnomAD)
- Structure
- AlphaFold pLDDT 74.53 · 38 PDB
- Residue 268
- the 'disordered' region
Similar variants
- PDCD1 c.437-115G>A Benign ★★ same type
- PDCD1 c.593-56C>G Benign ★★ same type
- PDCD1 c.627+189G>A Benign ★★ same type
- PDCD1 c.628-110A>G Benign ★★ same type
- PDCD1 c.76+126G>C Benign ★★ same type
- PDCD1 c.76+15C>T Benign ★★ same type
- PDCD1 c.*889G>A Benign ★★ same type
- PDCD1 p.Ala215Val Benign ★★ 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/pdcd1-p-ala268 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown