Is DSPP p.Asp169Asn (c.505G>A) pathogenic?

DSPP p.Asp169Asn (c.505G>A) is classified Uncertain significance in DSPP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0686); Ultra-rare (popmax 0.0213%, afr); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Asp169Asn (c.505G>A)?

DSPP p.Asp169Asn (c.505G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Asp169Asn (c.505G>A) in the general population?

DSPP p.Asp169Asn (c.505G>A) is ultra-rare (popmax 0.0213%, afr) (gnomAD).

What do computational predictors say about DSPP p.Asp169Asn (c.505G>A)?

AlphaMissense predicts likely benign (score 0.0686) — an in-silico prediction, not a clinical call.

DSPP p.Asp169Asn

c.505G>A · rs368559431 · VCV1806686

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0686 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0213%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0686	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -5.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.22	GERP -3.5
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	1.777	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0213% African / African-American · 16/74,948 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00242% 39/1,614,034 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0213%	4,684
Remaining individualsnot grpmax-eligible	0.0064%	15,623
Admixed American	0.005%	20,000
South Asian	0.00329%	30,357
East Asian	0.00223%	44,890
European (non-Finnish)	0.00102%	98,334

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.Asp169Asn
Coding: c.505G>A
dbSNP: rs368559431
Type: single nucleotide variant
Location: chr4:87612691 (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-asp169asn (accessed [today's date]).

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