Is DSPP p.Pro17Leu (c.50C>T) pathogenic?

DSPP p.Pro17Leu (c.50C>T) is classified Pathogenic in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). AlphaMissense: likely pathogenic (0.5648); Absent from gnomAD v4.1.

How common is DSPP p.Pro17Leu (c.50C>T) in the general population?

DSPP p.Pro17Leu (c.50C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSPP p.Pro17Leu (c.50C>T)?

AlphaMissense predicts likely pathogenic (score 0.5648) — an in-silico prediction, not a clinical call.

DSPP p.Pro17Leu

c.50C>T · rs2475879245 · VCV2734658

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5648 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5648	likely pathogenic ✓ concordant with ClinVar
REVEL	0.697	pathogenic-leaning
SaProt	LLR -9.96	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: DSPP
Protein: p.Pro17Leu
Coding: c.50C>T
dbSNP: rs2475879245
Type: single nucleotide variant
Location: chr4:87610958 (GRCh38)

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

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/dspp-p-pro17leu (accessed [today's date]).

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