Is DSPP p.Ser1208= (c.3624T>C) pathogenic?

DSPP p.Ser1208= (c.3624T>C) is classified Benign/Likely benign in DSPP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-03-08). Common (popmax 15.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Ser1208= (c.3624T>C)?

DSPP p.Ser1208= (c.3624T>C) is associated with Inborn genetic diseases (ClinVar).

DSPP p.Ser1208=

Q: How common is DSPP p.Ser1208= (c.3624T>C) in the general population?

DSPP p.Ser1208= (c.3624T>C) is common (popmax 15.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3624T>C · rs111536498 · VCV1242184

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 15.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

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 -20	GERP -3.1
Overall
CADD	0.199	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15.5% African / African-American · 6,438/41,570 alleles

Filtering AF 15.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 15%

Overall 1.8% 26,032/1,444,074 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	15.5%	6
Finnishnot grpmax-eligible	5.96%	17
Middle Eastern	2.75%	36
Ashkenazi Jewishnot grpmax-eligible	2.66%	38
Remaining individualsnot grpmax-eligible	2.46%	41
Admixed American	2.02%	50
South Asian	1.66%	60
European (non-Finnish)	1.07%	93
East Asian	0.42%	238

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.Ser1208=
Coding: c.3624T>C
dbSNP: rs111536498
Type: single nucleotide variant
Location: chr4:87616286 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-ser1208 (accessed [today's date]).

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