Is DSPP p.Ser1235= (c.3705C>T) pathogenic?

DSPP p.Ser1235= (c.3705C>T) is classified Likely benign in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-01). Ultra-rare (popmax 0.0199%, afr).

How common is DSPP p.Ser1235= (c.3705C>T) in the general population?

DSPP p.Ser1235= (c.3705C>T) is ultra-rare (popmax 0.0199%, afr) (gnomAD).

DSPP p.Ser1235=

c.3705C>T · VCV4820878

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0199%, afr)

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 -0.65	GERP -3.4, phastCons 0.006
Overall
CADD	0.432	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0199% African / African-American · 14/70,460 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00958%

Overall 0.00304% 46/1,512,570 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0199%	5,033
South Asian	0.0111%	8,987
East Asian	0.00768%	13,014
Remaining individualsnot grpmax-eligible	0.00515%	19,424
European (non-Finnish)	0.00151%	66,011

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.Ser1235=
Coding: c.3705C>T
MANE Select: NM_014208
Type: single nucleotide variant
Location: chr4:87616367 (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-ser1235 (accessed [today's date]).

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