Is DSPP p.Asp1077Asn (c.3229G>A) pathogenic?

DSPP p.Asp1077Asn (c.3229G>A) is classified Conflicting classifications of pathogenicity in DSPP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-11-09). AlphaMissense: likely benign (0.1146); Very rare (popmax 0.00435%, amr); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Asp1077Asn (c.3229G>A)?

DSPP p.Asp1077Asn (c.3229G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Asp1077Asn (c.3229G>A) in the general population?

DSPP p.Asp1077Asn (c.3229G>A) is very rare (popmax 0.00435%, amr) (gnomAD).

What do computational predictors say about DSPP p.Asp1077Asn (c.3229G>A)?

AlphaMissense predicts likely benign (score 0.1146) — an in-silico prediction, not a clinical call.

DSPP p.Asp1077Asn

c.3229G>A · rs1413376466 · VCV2213838

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1146 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00435%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1146	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -8.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.4	GERP -2
Regional constraint	o/e 0.38	unconstrained · MANE · 513 bp · p 9.7e-18 · regional, not allelic
Overall
CADD	13.99	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 0.00435% Admixed American · 2/45,954 alleles

Filtering AF 0.000985% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000473%

Overall 0.000731% 11/1,504,442 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00435%	22,977
South Asian	0.00371%	26,967
East Asian	0.00258%	38,706
European (non-Finnish)	0.000442%	226,097

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.Asp1077Asn
Coding: c.3229G>A
dbSNP: rs1413376466
Type: single nucleotide variant
Location: chr4:87615891 (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-asp1077asn (accessed [today's date]).

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