Is DSPP p.Ser1217= (c.3651T>C) pathogenic?

DSPP p.Ser1217= (c.3651T>C) is classified Likely benign in DSPP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-01). Very rare (popmax 0.00374%, sas).

How common is DSPP p.Ser1217= (c.3651T>C) in the general population?

DSPP p.Ser1217= (c.3651T>C) is very rare (popmax 0.00374%, sas) (gnomAD).

DSPP p.Ser1217=

c.3651T>C · VCV4533443

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00374%, sas)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

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 -10	GERP -0.99
Overall
CADD	0.151	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00374% South Asian · 3/80,280 alleles

Filtering AF 0.000992% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000475%

Overall 0.00067% 10/1,492,196 alleles · very rare exomes 8/1,361,720 · genomes 2/130,476 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00374%	26,760
Admixed American	0.00212%	47,098
European (non-Finnish)	0.000539%	185,394

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.Ser1217=
Coding: c.3651T>C
MANE Select: NM_014208
Type: single nucleotide variant
Location: chr4:87616313 (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-ser1217 (accessed [today's date]).

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