Is DSEL p.Pro507Leu (c.1520C>T) pathogenic?

DSEL p.Pro507Leu (c.1520C>T) is classified Uncertain significance in DSEL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-07). Absent from gnomAD v4.1.

How common is DSEL p.Pro507Leu (c.1520C>T) in the general population?

DSEL p.Pro507Leu (c.1520C>T) is absent from gnomAD v4.1 (gnomAD).

DSEL p.Pro507Leu

c.1520C>T · VCV4015003

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.345	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.16, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 2,707 bp · p 0.014 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DSEL
Protein: p.Pro507Leu
Coding: c.1520C>T
MANE Select: NM_032160
Type: single nucleotide variant
Location: chr18:67513089 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.75

Full DSEL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DSEL p.Pro942Ser Benign ★★ same type
DSEL p.Tyr730Cys Likely benign ★★ same type
DSEL c.-1C>G Uncertain significance ★ same type
DSEL p.Ala1110Val Uncertain significance ★ same type
DSEL p.Ala178Thr Uncertain significance ★ same type
DSEL p.Ala236Thr Uncertain significance ★ same type
DSEL p.Ala278Thr Uncertain significance ★ same type
DSEL p.Ala2Thr 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/dsel-p-pro507leu (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown