Is DSPP p.Glu47Lys (c.139G>A) pathogenic?

DSPP p.Glu47Lys (c.139G>A) is classified Conflicting classifications of pathogenicity in DSPP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-03-26). AlphaMissense: likely benign (0.0709); Very rare (popmax 0.00144%, nfe); Associated with dentinogenesis imperfecta type 2.

What condition is associated with DSPP p.Glu47Lys (c.139G>A)?

DSPP p.Glu47Lys (c.139G>A) is associated with dentinogenesis imperfecta type 2 (ClinVar).

How common is DSPP p.Glu47Lys (c.139G>A) in the general population?

DSPP p.Glu47Lys (c.139G>A) is very rare (popmax 0.00144%, nfe) (gnomAD).

How is Dentinogenesis imperfecta inherited?

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

What do computational predictors say about DSPP p.Glu47Lys (c.139G>A)?

AlphaMissense predicts likely benign (score 0.0709) — an in-silico prediction, not a clinical call.

DSPP p.Glu47Lys

c.139G>A · rs1218312896 · VCV2571632

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0709 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

dentinogenesis imperfecta type 2

Computational evidence

Protein change
AlphaMissense	0.0709	likely benign
REVEL	0.309	indeterminate
SaProt	LLR -6.66	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 0.99, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	18.94	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 0.00144% European (non-Finnish) · 17/1,179,966 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00105% 17/1,613,926 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.Glu47Lys
Coding: c.139G>A
MANE Select: NM_014208
dbSNP: rs1218312896
Type: single nucleotide variant
Location: chr4:87612325 (GRCh38)
Gene constraint: LOEUF 1.271 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 39.36

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.Glu511Ter Likely pathogenic ★ 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-glu47lys (accessed [today's date]).

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