Is DSPP p.Ala13Pro (c.37G>C) pathogenic?

DSPP p.Ala13Pro (c.37G>C) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-16). AlphaMissense: likely pathogenic (0.9035); Very rare (popmax 8.48e-05%, nfe).

How common is DSPP p.Ala13Pro (c.37G>C) in the general population?

DSPP p.Ala13Pro (c.37G>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DSPP p.Ala13Pro (c.37G>C)?

AlphaMissense predicts likely pathogenic (score 0.9035) — an in-silico prediction, not a clinical call.

DSPP p.Ala13Pro

c.37G>C · rs2109994819 · VCV1372943

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9035 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9035	likely pathogenic
REVEL	0.492	indeterminate
SaProt	LLR -9.93	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.8	GERP 0.95, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	19.73	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 8.48e-05% European (non-Finnish) · 1/1,179,626 alleles

Overall 6.84e-05% 1/1,461,454 alleles · very rare

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.Ala13Pro
Coding: c.37G>C
dbSNP: rs2109994819
Type: single nucleotide variant
Location: chr4:87610945 (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-ala13pro (accessed [today's date]).

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