Is DSPP p.Asn1122Asp (c.3364A>G) pathogenic?

DSPP p.Asn1122Asp (c.3364A>G) is classified Likely benign in DSPP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-11-10). AlphaMissense: likely benign (0.0612); Rare (popmax 0.633%, afr).

How common is DSPP p.Asn1122Asp (c.3364A>G) in the general population?

DSPP p.Asn1122Asp (c.3364A>G) is rare (popmax 0.633%, afr) (gnomAD).

What do computational predictors say about DSPP p.Asn1122Asp (c.3364A>G)?

AlphaMissense predicts likely benign (score 0.0612) — an in-silico prediction, not a clinical call.

DSPP p.Asn1122Asp

c.3364A>G · rs201399566 · VCV1182318

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0612 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.633%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0612	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -4.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -4	GERP -2.4
Regional constraint	o/e 0.38	unconstrained · MANE · 513 bp · p 9.7e-18 · regional, not allelic
Overall
CADD	0.41	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 0.633% African / African-American · 49/7,736 alleles

Filtering AF 0.492% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.442%

Overall 0.0982% 305/310,500 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.47%	68
African / African-Americangrpmax	0.633%	158
East Asian	0.612%	163
Finnishnot grpmax-eligible	0.337%	297
Remaining individualsnot grpmax-eligible	0.129%	778
Admixed American	0.0913%	1,096
European (non-Finnish)	0.0742%	1,349
Ashkenazi Jewishnot grpmax-eligible	0.0695%	1,439
South Asian	0.0618%	1,617

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asn1122Asp
Coding: c.3364A>G
dbSNP: rs201399566
Type: single nucleotide variant
Location: chr4:87616026 (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-asn1122asp (accessed [today's date]).

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