Is DSPP p.Glu1149Asp (c.3447A>T) pathogenic?

DSPP p.Glu1149Asp (c.3447A>T) is classified Benign/Likely benign in DSPP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-16). AlphaMissense: likely benign (0.0282); Low-frequency (popmax 3.94%, eas).

How common is DSPP p.Glu1149Asp (c.3447A>T) in the general population?

DSPP p.Glu1149Asp (c.3447A>T) is low-frequency (popmax 3.94%, eas) (gnomAD).

What do computational predictors say about DSPP p.Glu1149Asp (c.3447A>T)?

AlphaMissense predicts likely benign (score 0.0282) — an in-silico prediction, not a clinical call.

DSPP p.Glu1149Asp

c.3447A>T · rs200612038 · VCV2428521

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0282 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.94%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0282	likely benign
REVEL	0.215	benign-leaning
SaProt	LLR -0.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -20	GERP -2.1
Regional constraint	o/e 0.38	unconstrained · MANE · 513 bp · p 9.7e-18 · regional, not allelic
Overall
CADD	0.572	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 3.94% East Asian · 346/8,780 alleles

Filtering AF 3.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.46%

Overall 0.786% 4,678/595,526 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	3.94%	25
Admixed American	2.11%	47
South Asian	1.56%	64
Finnishnot grpmax-eligible	1.49%	67
Remaining individualsnot grpmax-eligible	0.96%	104
European (non-Finnish)	0.603%	166
Middle Eastern	0.55%	182
Ashkenazi Jewishnot grpmax-eligible	0.488%	205
African / African-American	0.311%	321

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.Glu1149Asp
Coding: c.3447A>T
dbSNP: rs200612038
Type: single nucleotide variant
Location: chr4:87616109 (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-glu1149asp (accessed [today's date]).

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