PDSS2 p.Val226=
c.678A>G · rs142774321 · VCV508410
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0147%, sas)
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 -0.39 | GERP -1.6, phastCons 0.22 |
| Overall | ||
| CADD | 2.559 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0147%
South Asian · 13/88,318 alleles
Filtering AF
0.00869%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0069%
Overall
0.00107%
17/1,590,806 alleles · ultra-rare
exomes 15/1,438,622 · genomes 2/152,184 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0147% | 6,794 |
| East Asian | 0.00898% | 11,136 |
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
- PDSS2
- Protein
- p.Val226=
- Coding
- c.678A>G
- MANE Select
- NM_020381
- dbSNP
- rs142774321
- Type
- single nucleotide variant
- Location
- chr6:107245572 (GRCh38)
- Gene constraint
- LOEUF 0.818 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 80.28
Similar variants
- PDSS2 p.Arg163His Uncertain significance ★★ ⚠ same type
- PDSS2 p.Arg366Cys Uncertain significance ★★ ⚠ same type
- PDSS2 p.Arg366His Uncertain significance ★★ ⚠ same type
- PDSS2 p.Arg385Thr Uncertain significance ★★ ⚠ same type
- PDSS2 p.Asn167Ser Uncertain significance ★★ ⚠ same type
- PDSS2 p.Asn201Ser Uncertain significance ★★ ⚠ same type
- PDSS2 p.Asn314Thr Uncertain significance ★★ ⚠ same type
- PDSS2 p.Asn390Ser 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/pdss2-p-val226 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown