Is DSPP p.Ser776Ile (c.2327G>T) pathogenic?

DSPP p.Ser776Ile (c.2327G>T) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely benign (0.2749); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Ser776Ile (c.2327G>T)?

DSPP p.Ser776Ile (c.2327G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Ser776Ile (c.2327G>T) in the general population?

DSPP p.Ser776Ile (c.2327G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSPP p.Ser776Ile (c.2327G>T)?

AlphaMissense predicts likely benign (score 0.2749) — an in-silico prediction, not a clinical call.

DSPP p.Ser776Ile

c.2327G>T · VCV4245174

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2749 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2749	likely benign
REVEL	0.295	indeterminate
SaProt	LLR -11.78	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.66	GERP -1.1, phastCons 0.001
Regional constraint	o/e 0.73	unconstrained · MANE · 1,389 bp · p 1.3e-11 · regional, not allelic
Overall
CADD	12.01	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DSPP
Protein: p.Ser776Ile
Coding: c.2327G>T
MANE Select: NM_014208
Type: single nucleotide variant
Location: chr4:87614989 (GRCh38)
Gene constraint: LOEUF 1.271 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 39.36
Residue 776: the 'disordered' region

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

Similar variants

DSPP p.Arg354Leu Uncertain significance ★ ⚠ same condition
DSPP p.Asp1086Gly Uncertain significance ★ ⚠ same condition
DSPP p.Asp1152Glu Uncertain significance ★ ⚠ same condition
DSPP p.Asp1173Asn Uncertain significance ★ ⚠ same condition
DSPP p.Asp843Asn Uncertain significance ★ ⚠ same condition
DSPP p.Asp896Glu Uncertain significance ★ ⚠ same condition
DSPP p.Glu1083Gln Uncertain significance ★ ⚠ same condition
DSPP p.Ile142Ser Uncertain significance ★ ⚠ same condition

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-ser776ile (accessed [today's date]).

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