Is DSPP p.Thr210Pro (c.628A>C) pathogenic?

DSPP p.Thr210Pro (c.628A>C) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-03). AlphaMissense: likely benign (0.1259); Very rare (popmax 6.84e-05%).

How common is DSPP p.Thr210Pro (c.628A>C) in the general population?

DSPP p.Thr210Pro (c.628A>C) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about DSPP p.Thr210Pro (c.628A>C)?

AlphaMissense predicts likely benign (score 0.1259) — an in-silico prediction, not a clinical call.

DSPP p.Thr210Pro

c.628A>C · VCV3379546

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1259 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1259	likely benign
REVEL	0.343	indeterminate
SaProt	LLR -7.35	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.13	GERP -3.7
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	6.678	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,872 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.Thr210Pro
Coding: c.628A>C
Type: single nucleotide variant
Location: chr4:87612814 (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-thr210pro (accessed [today's date]).

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