Is DSPP p.Ser299= (c.897A>G) pathogenic?

DSPP p.Ser299= (c.897A>G) is classified Benign in DSPP (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 73.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with deafness, autosomal dominant 39, with dentinogenesis imperfecta 1.

What condition is associated with DSPP p.Ser299= (c.897A>G)?

DSPP p.Ser299= (c.897A>G) is associated with deafness, autosomal dominant 39, with dentinogenesis imperfecta 1, dentinogenesis imperfecta type 2, dentinogenesis imperfecta type 3 (ClinVar).

DSPP p.Ser299=

Q: How common is DSPP p.Ser299= (c.897A>G) in the general population?

DSPP p.Ser299= (c.897A>G) is common (popmax 73.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.897A>G · rs2736982 · VCV260359

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 73.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

deafness, autosomal dominant 39, with dentinogenesis imperfecta 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.2	GERP -3
Overall
CADD	0.763	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 73.5% African / African-American · 55,019/74,882 alleles

Filtering AF 73% ClinGen BA1/BS1 input FAF95, joint · FAF99 72.7%

Overall 61.5% 993,294/1,613,822 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	73.5%	1
Finnishnot grpmax-eligible	68.1%	1
Middle Eastern	67.7%	1
East Asian	64.4%	2
Remaining individualsnot grpmax-eligible	62%	2
European (non-Finnish)	60.8%	2
Admixed American	59.8%	2
South Asian	57.9%	2
Ashkenazi Jewishnot grpmax-eligible	56.9%	2
Amishnot grpmax-eligible	52.6%	2

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.Ser299=
Coding: c.897A>G
dbSNP: rs2736982
Type: single nucleotide variant
Location: chr4:87613083 (GRCh38)

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

Disease context

deafness, autosomal dominant 39, with dentinogenesis imperfecta 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dentinogenesis imperfecta type 2 dentinogenesis imperfecta type 3

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-ser299 (accessed [today's date]).

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