Is DSPP p.Asp1104Glu (c.3312C>A) pathogenic?

DSPP p.Asp1104Glu (c.3312C>A) is classified Likely benign in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). AlphaMissense: ambiguous (0.3594); Rare (popmax 0.655%, afr).

How common is DSPP p.Asp1104Glu (c.3312C>A) in the general population?

DSPP p.Asp1104Glu (c.3312C>A) is rare (popmax 0.655%, afr) (gnomAD).

What do computational predictors say about DSPP p.Asp1104Glu (c.3312C>A)?

AlphaMissense predicts ambiguous (score 0.3594) — an in-silico prediction, not a clinical call.

DSPP p.Asp1104Glu

c.3312C>A · rs766191304 · VCV2654908

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3594 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.655%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3594	ambiguous
REVEL	0.224	benign-leaning
SaProt	LLR -9.97	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -20	GERP -0.86
Regional constraint	o/e 0.38	unconstrained · MANE · 513 bp · p 9.7e-18 · regional, not allelic
Overall
CADD	8.149	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 0.655% African / African-American · 83/12,666 alleles

Filtering AF 0.542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.5%

Overall 0.106% 494/467,364 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.655%	153
Middle Eastern	0.585%	171
Remaining individualsnot grpmax-eligible	0.211%	474
South Asian	0.175%	571
Ashkenazi Jewishnot grpmax-eligible	0.171%	585
Admixed American	0.138%	723
European (non-Finnish)	0.0661%	1,512
Finnishnot grpmax-eligible	0.0471%	2,124
East Asian	0.0437%	2,291

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.Asp1104Glu
Coding: c.3312C>A
dbSNP: rs766191304
Type: single nucleotide variant
Location: chr4:87615974 (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-asp1104glu (accessed [today's date]).

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