Is DSPP p.Ser780Arg (c.2340C>A) pathogenic?

DSPP p.Ser780Arg (c.2340C>A) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: ambiguous (0.4981); Very rare (popmax 0.00555%, afr); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Ser780Arg (c.2340C>A)?

DSPP p.Ser780Arg (c.2340C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Ser780Arg (c.2340C>A) in the general population?

DSPP p.Ser780Arg (c.2340C>A) is very rare (popmax 0.00555%, afr) (gnomAD).

What do computational predictors say about DSPP p.Ser780Arg (c.2340C>A)?

AlphaMissense predicts ambiguous (score 0.4981) — an in-silico prediction, not a clinical call.

DSPP p.Ser780Arg

c.2340C>A · VCV4618028

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4981 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00555%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.4981	ambiguous
REVEL	0.275	benign-leaning
SaProt	LLR -12.43	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -4.5	GERP -1.4
Regional constraint	o/e 0.73	unconstrained · MANE · 1,389 bp · p 1.3e-11 · regional, not allelic
Overall
CADD	0.447	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 0.00555% African / African-American · 4/72,012 alleles

Filtering AF 0.0019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00107%

Overall 0.000387% 6/1,548,692 alleles · very rare exomes 3/1,399,088 · genomes 3/149,604 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00555%	18,003
Admixed American	0.00197%	50,750
Remaining individualsnot grpmax-eligible	0.00167%	60,034

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.Ser780Arg
Coding: c.2340C>A
MANE Select: NM_014208
Type: single nucleotide variant
Location: chr4:87615002 (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-ser780arg (accessed [today's date]).

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