Is DSPP p.Pro17Ser (c.49C>T) pathogenic?

DSPP p.Pro17Ser (c.49C>T) is classified Pathogenic in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-14). AlphaMissense: ambiguous (0.5512); Very rare (popmax 0.00134%, afr).

How common is DSPP p.Pro17Ser (c.49C>T) in the general population?

DSPP p.Pro17Ser (c.49C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about DSPP p.Pro17Ser (c.49C>T)?

AlphaMissense predicts ambiguous (score 0.5512) — an in-silico prediction, not a clinical call.

DSPP p.Pro17Ser

c.49C>T · rs121912986 · VCV1458861

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5512 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.5512	ambiguous
REVEL	0.6	indeterminate
SaProt	LLR -10.32	damaging
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	28.4	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

Grpmax group 0.00134% African / African-American · 1/74,762 alleles

Overall 6.2e-05% 1/1,612,840 alleles · very rare exomes 1/1,461,168 · genomes 0/151,672 · 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: DSPP
Protein: p.Pro17Ser
Coding: c.49C>T
MANE Select: NM_014208
dbSNP: rs121912986
Type: single nucleotide variant
Location: chr4:87610957 (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-pro17ser (accessed [today's date]).

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