Is DSPP p.Asp946Tyr (c.2836G>T) pathogenic?

DSPP p.Asp946Tyr (c.2836G>T) is classified Uncertain significance in DSPP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-03). AlphaMissense: likely benign (0.3398); Ultra-rare (popmax 0.0167%, mid); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Asp946Tyr (c.2836G>T)?

DSPP p.Asp946Tyr (c.2836G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Asp946Tyr (c.2836G>T) in the general population?

DSPP p.Asp946Tyr (c.2836G>T) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

What do computational predictors say about DSPP p.Asp946Tyr (c.2836G>T)?

AlphaMissense predicts likely benign (score 0.3398) — an in-silico prediction, not a clinical call.

DSPP p.Asp946Tyr

c.2836G>T · rs370270012 · VCV2231201

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3398 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3398	likely benign
REVEL	0.222	benign-leaning
SaProt	LLR -13.27	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 -2.6	GERP -0.96
Regional constraint	o/e 0.73	unconstrained · MANE · 1,389 bp · p 1.3e-11 · regional, not allelic
Overall
CADD	12.76	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 0.0167% Middle Eastern · 1/5,990 alleles

Filtering AF 0.00142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00119%

Overall 0.00182% 28/1,538,388 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,990
Remaining individualsnot grpmax-eligible	0.00336%	29,776
European (non-Finnish)	0.00209%	47,751
Admixed American	0.00199%	50,172

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.Asp946Tyr
Coding: c.2836G>T
dbSNP: rs370270012
Type: single nucleotide variant
Location: chr4:87615498 (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-asp946tyr (accessed [today's date]).

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