Is DSPP p.Glu342Lys (c.1024G>A) pathogenic?

DSPP p.Glu342Lys (c.1024G>A) is classified Conflicting classifications of pathogenicity in DSPP (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-08-18). AlphaMissense: likely benign (0.0917); Ultra-rare (popmax 0.0417%, amr); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Glu342Lys (c.1024G>A)?

DSPP p.Glu342Lys (c.1024G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Glu342Lys (c.1024G>A) in the general population?

DSPP p.Glu342Lys (c.1024G>A) is ultra-rare (popmax 0.0417%, amr) (gnomAD).

What do computational predictors say about DSPP p.Glu342Lys (c.1024G>A)?

AlphaMissense predicts likely benign (score 0.0917) — an in-silico prediction, not a clinical call.

DSPP p.Glu342Lys

c.1024G>A · rs201404949 · VCV1185809

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0917 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0417%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0917	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -6.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.9	GERP 0.59, phastCons 0.027
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	17.48	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 0.0417% Admixed American · 25/59,998 alleles

Filtering AF 0.0376% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0364%

Overall 0.0335% 540/1,613,898 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0417%	2,400
Remaining individualsnot grpmax-eligible	0.0416%	2,403
European (non-Finnish)	0.0406%	2,464
African / African-American	0.0133%	7,492

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.Glu342Lys
Coding: c.1024G>A
MANE Select: NM_014208
dbSNP: rs201404949
Type: single nucleotide variant
Location: chr4:87613210 (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-glu342lys (accessed [today's date]).

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