Is DSPP p.Glu511Ter (c.1531G>T) pathogenic?

DSPP p.Glu511Ter (c.1531G>T) is classified Likely pathogenic in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-18). Very rare (popmax 0.00133%, afr); Associated with dentinogenesis imperfecta type 2.

What condition is associated with DSPP p.Glu511Ter (c.1531G>T)?

DSPP p.Glu511Ter (c.1531G>T) is associated with dentinogenesis imperfecta type 2 (ClinVar).

How common is DSPP p.Glu511Ter (c.1531G>T) in the general population?

DSPP p.Glu511Ter (c.1531G>T) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Dentinogenesis imperfecta inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

DSPP p.Glu511Ter

c.1531G>T · VCV3775878

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

dentinogenesis imperfecta type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (5 of 5) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 0.36, phastCons 0.99
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,950 alleles

Overall 0.000124% 2/1,614,132 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,950
European (non-Finnish)	8.47e-05%	1,180,043

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.Glu511Ter
Coding: c.1531G>T
MANE Select: NM_014208
Type: single nucleotide variant
Location: chr4:87614193 (GRCh38)
Gene constraint: LOEUF 1.271 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 39.36
Residue 511: the 'disordered' region

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

Disease context

dentinogenesis imperfecta type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dentinogenesis imperfecta (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

DSPP p.Glu327Asp Uncertain significance ★★ ⚠ same condition
DSPP p.Glu47Lys Conflicting classifications of pathogenicity ★ ⚠ same condition
DSPP p.Ser1180fs Pathogenic ★ same condition
DSPP p.Ser1204fs Likely pathogenic ★ same condition
DSPP p.Ser945fs Likely pathogenic same condition
DSPP p.Arg354Leu Uncertain significance ★ ⚠ same type
DSPP p.Asp1086Gly Uncertain significance ★ ⚠ same type
DSPP p.Asp1152Glu 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/dspp-p-glu511ter (accessed [today's date]).

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