PSEN1 p.Val142=
c.426C>T · rs2503075929 · VCV2068659
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
Conditions
4
frontotemporal dementia
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 1.8 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 11.03 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/60,008 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000124%
2/1,613,914 alleles · very rare
exomes 2/1,461,660 · genomes 0/152,254 · joint denominator
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
- PSEN1
- Protein
- p.Val142=
- Coding
- c.426C>T
- MANE Select
- NM_000021
- dbSNP
- rs2503075929
- Type
- single nucleotide variant
- Location
- chr14:73173653 (GRCh38)
- Gene constraint
- LOEUF 0.425 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 72.27 · 27 PDB
- Residue 142
- an α-helix; a UniProt-annotated variant site (in ad3; uncertain significance)
Similar variants
- PSEN1 p.Val142Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
- PSEN1 c.869-1G>A Pathogenic/Likely pathogenic ★★ same condition
- PSEN1 p.Ala231Thr Likely pathogenic ★★ same condition
- PSEN1 p.Ala246Glu Pathogenic ★★ same condition
- PSEN1 p.Ala285Val Pathogenic ★★ same condition
- PSEN1 p.Ala426Pro Pathogenic/Likely pathogenic ★★ same condition
- PSEN1 p.Ala431Glu Pathogenic ★★ same condition
- PSEN1 p.Ala79Val Pathogenic ★★ same condition
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/psen1-p-val142 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown