PDSS2 p.Ser42=
c.126C>T · rs139424190 · VCV2052859
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.005%, 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 -0.052 | GERP -3.4, phastCons 0.22 |
| Overall | ||
| CADD | 8.399 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
European (non-Finnish) · 59/1,180,052 alleles
Filtering AF
0.00394%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00361%
Overall
0.00372%
60/1,614,064 alleles · very rare
exomes 56/1,461,864 · genomes 4/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.005% | 20,001 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,490 |
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.Ser42=
- Coding
- c.126C>T
- MANE Select
- NM_020381
- dbSNP
- rs139424190
- Type
- single nucleotide variant
- Location
- chr6:107459160 (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.Ser42Phe Uncertain significance ★★ ⚠ same residue
- 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
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-ser42 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown