Is DSPP p.Asp1107Glu (c.3321T>A) pathogenic?

DSPP p.Asp1107Glu (c.3321T>A) is classified Benign in DSPP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-11-10). AlphaMissense: likely benign (0.2886); Common (popmax 8.95%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about DSPP p.Asp1107Glu (c.3321T>A)?

AlphaMissense predicts likely benign (score 0.2886) — an in-silico prediction, not a clinical call.

DSPP p.Asp1107Glu

Q: How common is DSPP p.Asp1107Glu (c.3321T>A) in the general population?

DSPP p.Asp1107Glu (c.3321T>A) is common (popmax 8.95%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3321T>A · rs374679002 · VCV1247713

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2886 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.95%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2886	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -9.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -12	GERP -2
Regional constraint	o/e 0.38	unconstrained · MANE · 513 bp · p 9.7e-18 · regional, not allelic
Overall
CADD	7.64	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.95% East Asian · 1,218/13,614 alleles

Filtering AF 8.53% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.36%

Overall 2.74% 12,154/443,780 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	8.95%	11
Finnishnot grpmax-eligible	5.94%	17
African / African-American	3.74%	27
Remaining individualsnot grpmax-eligible	3.72%	27
Admixed American	3.25%	31
Middle Eastern	2.4%	42
European (non-Finnish)	2.35%	43
Ashkenazi Jewishnot grpmax-eligible	2.18%	46
South Asian	1.27%	79

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.Asp1107Glu
Coding: c.3321T>A
dbSNP: rs374679002
Type: single nucleotide variant
Location: chr4:87615983 (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-asp1107glu (accessed [today's date]).

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