Is DSPP p.Asp464Glu (c.1392T>A) pathogenic?

DSPP p.Asp464Glu (c.1392T>A) is classified Uncertain significance in DSPP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-24). AlphaMissense: likely benign (0.2964); Ultra-rare (popmax 0.0822%, mid).

How common is DSPP p.Asp464Glu (c.1392T>A) in the general population?

DSPP p.Asp464Glu (c.1392T>A) is ultra-rare (popmax 0.0822%, mid) (gnomAD).

What do computational predictors say about DSPP p.Asp464Glu (c.1392T>A)?

AlphaMissense predicts likely benign (score 0.2964) — an in-silico prediction, not a clinical call.

DSPP p.Asp464Glu

c.1392T>A · rs750248048 · VCV2663045

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2964 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0822%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2964	likely benign
REVEL	0.471	indeterminate
SaProt	LLR -7.20	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -3.3	GERP -2.6
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	12.46	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 0.0822% Middle Eastern · 5/6,084 alleles

Filtering AF 0.0323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.00173% 28/1,614,084 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0822%	1,217
African / African-American	0.00801%	12,488
Remaining individualsnot grpmax-eligible	0.008%	12,498
South Asian	0.0011%	91,086
European (non-Finnish)	0.000932%	107,277

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.Asp464Glu
Coding: c.1392T>A
dbSNP: rs750248048
Type: single nucleotide variant
Location: chr4:87614054 (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-asp464glu (accessed [today's date]).

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