Is DSPP p.Ser1072Arg (c.3214A>C) pathogenic?

DSPP p.Ser1072Arg (c.3214A>C) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-23). AlphaMissense: likely pathogenic (0.7532); Very rare (popmax 0.00122%, sas); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Ser1072Arg (c.3214A>C)?

DSPP p.Ser1072Arg (c.3214A>C) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Ser1072Arg (c.3214A>C) in the general population?

DSPP p.Ser1072Arg (c.3214A>C) is very rare (popmax 0.00122%, sas) (gnomAD).

What do computational predictors say about DSPP p.Ser1072Arg (c.3214A>C)?

AlphaMissense predicts likely pathogenic (score 0.7532) — an in-silico prediction, not a clinical call.

DSPP p.Ser1072Arg

c.3214A>C · VCV3842730

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7532 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00122%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7532	likely pathogenic
REVEL	0.234	benign-leaning
SaProt	LLR -11.81	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.7	GERP 1, phastCons 0.46
Regional constraint	o/e 0.38	unconstrained · MANE · 513 bp · p 9.7e-18 · regional, not allelic
Overall
CADD	17.6	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 0.00122% South Asian · 1/82,076 alleles

Overall 7.19e-05% 1/1,391,076 alleles · very rare

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.Ser1072Arg
Coding: c.3214A>C
Type: single nucleotide variant
Location: chr4:87615876 (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-ser1072arg (accessed [today's date]).

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