Is DSPP p.Ser1157= (c.3471C>T) pathogenic?

DSPP p.Ser1157= (c.3471C>T) is classified Likely benign in DSPP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-26). Ultra-rare (popmax 0.0143%, amr).

How common is DSPP p.Ser1157= (c.3471C>T) in the general population?

DSPP p.Ser1157= (c.3471C>T) is ultra-rare (popmax 0.0143%, amr) (gnomAD).

DSPP p.Ser1157=

c.3471C>T · rs761190313 · VCV2654920

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, amr)

⚠ 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 -8.2	GERP -1.7
Overall
CADD	1.229	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0143% Admixed American · 7/48,802 alleles

Filtering AF 0.00664% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00471%

Overall 0.00287% 44/1,531,254 alleles · ultra-rare exomes 36/1,390,914 · genomes 8/140,340 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0143%	6,972
African / African-American	0.00726%	13,770
East Asian	0.005%	19,995
South Asian	0.00365%	27,361
Finnishnot grpmax-eligible	0.00346%	28,915
European (non-Finnish)	0.00211%	47,474
Remaining individualsnot grpmax-eligible	0.00168%	59,394

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.Ser1157=
Coding: c.3471C>T
MANE Select: NM_014208
dbSNP: rs761190313
Type: single nucleotide variant
Location: chr4:87616133 (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-ser1157 (accessed [today's date]).

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