Is DSPP p.Asn1140Ser (c.3419A>G) pathogenic?

DSPP p.Asn1140Ser (c.3419A>G) is classified Conflicting classifications of pathogenicity in DSPP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-03). AlphaMissense: likely benign (0.1); Ultra-rare (popmax 0.0374%, amr); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Asn1140Ser (c.3419A>G)?

DSPP p.Asn1140Ser (c.3419A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Asn1140Ser (c.3419A>G) in the general population?

DSPP p.Asn1140Ser (c.3419A>G) is ultra-rare (popmax 0.0374%, amr) (gnomAD).

What do computational predictors say about DSPP p.Asn1140Ser (c.3419A>G)?

AlphaMissense predicts likely benign (score 0.1) — an in-silico prediction, not a clinical call.

DSPP p.Asn1140Ser

c.3419A>G · rs1215363888 · VCV2560154

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0374%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -10.09	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.7	GERP -0.001, phastCons 0.23
Regional constraint	o/e 0.38	unconstrained · MANE · 513 bp · p 9.7e-18 · regional, not allelic
Overall
CADD	13.26	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 0.0374% Admixed American · 15/40,056 alleles

Filtering AF 0.0231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0186%

Overall 0.0085% 114/1,341,780 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0374%	2,670
Finnishnot grpmax-eligible	0.0367%	2,724
South Asian	0.0305%	3,281
Remaining individualsnot grpmax-eligible	0.00904%	11,061
Ashkenazi Jewishnot grpmax-eligible	0.00776%	12,891
European (non-Finnish)	0.00452%	22,104
East Asian	0.00323%	30,932

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.Asn1140Ser
Coding: c.3419A>G
dbSNP: rs1215363888
Type: single nucleotide variant
Location: chr4:87616081 (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-asn1140ser (accessed [today's date]).

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