Is DSPP p.Thr389Ile (c.1166C>T) pathogenic?

DSPP p.Thr389Ile (c.1166C>T) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.2682); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Thr389Ile (c.1166C>T)?

DSPP p.Thr389Ile (c.1166C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Thr389Ile (c.1166C>T) in the general population?

DSPP p.Thr389Ile (c.1166C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about DSPP p.Thr389Ile (c.1166C>T)?

AlphaMissense predicts likely benign (score 0.2682) — an in-silico prediction, not a clinical call.

DSPP p.Thr389Ile

c.1166C>T · VCV4618034

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2682 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2682	likely benign
REVEL	0.399	indeterminate
SaProt	LLR -6.32	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.6	GERP -0.47, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	16.37	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,066 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000684% 10/1,461,854 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,533
European (non-Finnish)	0.000678%	147,501

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.Thr389Ile
Coding: c.1166C>T
Type: single nucleotide variant
Location: chr4:87613828 (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-thr389ile (accessed [today's date]).

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