Is DSPP p.Ser608Ile (c.1823G>T) pathogenic?

DSPP p.Ser608Ile (c.1823G>T) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: ambiguous (0.3482); Very rare (popmax 0.00209%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Ser608Ile (c.1823G>T)?

DSPP p.Ser608Ile (c.1823G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Ser608Ile (c.1823G>T) in the general population?

DSPP p.Ser608Ile (c.1823G>T) is very rare (popmax 0.00209%, nfe) (gnomAD).

What do computational predictors say about DSPP p.Ser608Ile (c.1823G>T)?

AlphaMissense predicts ambiguous (score 0.3482) — an in-silico prediction, not a clinical call.

DSPP p.Ser608Ile

c.1823G>T · VCV4015127

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3482 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00209%, nfe)

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	0.3482	ambiguous
REVEL	0.268	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 -0.27	GERP 0.45, phastCons 0.001
Regional constraint	o/e 0.73	unconstrained · MANE · 1,389 bp · p 1.3e-11 · regional, not allelic
Overall
CADD	13.8	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 0.00209% European (non-Finnish) · 24/1,147,026 alleles

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

Overall 0.00168% 26/1,551,634 alleles · very rare exomes 22/1,399,448 · genomes 4/152,186 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00209%	47,793
Admixed American	0.00196%	50,994
Remaining individualsnot grpmax-eligible	0.00166%	60,086

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.Ser608Ile
Coding: c.1823G>T
MANE Select: NM_014208
Type: single nucleotide variant
Location: chr4:87614485 (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-ser608ile (accessed [today's date]).

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