Is DSPP p.Glu1233Asp (c.3699A>C) pathogenic?

DSPP p.Glu1233Asp (c.3699A>C) is classified Benign/Likely benign in DSPP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-11-26). AlphaMissense: likely benign (0.0492); Common (popmax 16%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about DSPP p.Glu1233Asp (c.3699A>C)?

AlphaMissense predicts likely benign (score 0.0492) — an in-silico prediction, not a clinical call.

DSPP p.Glu1233Asp

Q: How common is DSPP p.Glu1233Asp (c.3699A>C) in the general population?

DSPP p.Glu1233Asp (c.3699A>C) is common (popmax 16%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3699A>C · rs112275895 · VCV1206199

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0492 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 16%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0492	likely benign
REVEL	0.229	benign-leaning
SaProt	LLR -2.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1	GERP -3, phastCons 0.006
Regional constraint	o/e 0.72	unconstrained · MANE · 391 bp · p 0.00018 · regional, not allelic
Overall
CADD	0.001	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 16% African / African-American · 5,960/37,194 alleles

Filtering AF 15.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 15.5%

Overall 1.7% 22,010/1,297,080 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	16%	6
Finnishnot grpmax-eligible	5.16%	19
Ashkenazi Jewishnot grpmax-eligible	3.04%	33
Middle Eastern	2.72%	37
Remaining individualsnot grpmax-eligible	2.38%	42
Admixed American	2.11%	47
South Asian	1.72%	58
European (non-Finnish)	0.947%	106
East Asian	0.509%	196
Amishnot grpmax-eligible	0.224%	446

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.Glu1233Asp
Coding: c.3699A>C
dbSNP: rs112275895
Type: single nucleotide variant
Location: chr4:87616361 (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-glu1233asp (accessed [today's date]).

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