Is DSPP p.Asp1155Glu (c.3465C>A) pathogenic?

DSPP p.Asp1155Glu (c.3465C>A) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-04). AlphaMissense: likely benign (0.2409); Ultra-rare (popmax 0.0389%, afr); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Asp1155Glu (c.3465C>A)?

DSPP p.Asp1155Glu (c.3465C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Asp1155Glu (c.3465C>A) in the general population?

DSPP p.Asp1155Glu (c.3465C>A) is ultra-rare (popmax 0.0389%, afr) (gnomAD).

What do computational predictors say about DSPP p.Asp1155Glu (c.3465C>A)?

AlphaMissense predicts likely benign (score 0.2409) — an in-silico prediction, not a clinical call.

DSPP p.Asp1155Glu

c.3465C>A · rs111216224 · VCV3086019

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2409 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0389%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2409	likely benign
REVEL	0.242	benign-leaning
SaProt	LLR -10.04	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -6.3	GERP -2.4
Regional constraint	o/e 0.38	unconstrained · MANE · 513 bp · p 9.7e-18 · regional, not allelic
Overall
CADD	0.009	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 0.0389% African / African-American · 16/41,154 alleles

Filtering AF 0.0243% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0198%

Overall 0.00855% 40/467,836 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0389%	2,572
Admixed American	0.017%	5,881
Ashkenazi Jewishnot grpmax-eligible	0.00902%	11,090
South Asian	0.00785%	12,732
Remaining individualsnot grpmax-eligible	0.00506%	19,780
Finnishnot grpmax-eligible	0.00497%	20,130
European (non-Finnish)	0.00496%	20,156

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.Asp1155Glu
Coding: c.3465C>A
dbSNP: rs111216224
Type: single nucleotide variant
Location: chr4:87616127 (GRCh38)

Full DSPP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-asp1155glu (accessed [today's date]).

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