Is DSPP p.Ile143Thr (c.428T>C) pathogenic?

DSPP p.Ile143Thr (c.428T>C) is classified Uncertain significance in DSPP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-03). AlphaMissense: likely benign (0.0639); Ultra-rare (popmax 0.0383%, amr); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Ile143Thr (c.428T>C)?

DSPP p.Ile143Thr (c.428T>C) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Ile143Thr (c.428T>C) in the general population?

DSPP p.Ile143Thr (c.428T>C) is ultra-rare (popmax 0.0383%, amr) (gnomAD).

What do computational predictors say about DSPP p.Ile143Thr (c.428T>C)?

AlphaMissense predicts likely benign (score 0.0639) — an in-silico prediction, not a clinical call.

DSPP p.Ile143Thr

c.428T>C · rs764136654 · VCV2212650

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0639 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0383%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0639	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -5.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -3.1	GERP -3.7
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	0.432	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 0.0383% Admixed American · 23/59,988 alleles

Filtering AF 0.0261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0222%

Overall 0.0018% 29/1,613,924 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0383%	2,608
African / African-American	0.00267%	37,452
East Asian	0.00223%	44,882
South Asian	0.0011%	91,068
European (non-Finnish)	0.000169%	589,988

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.Ile143Thr
Coding: c.428T>C
dbSNP: rs764136654
Type: single nucleotide variant
Location: chr4:87612614 (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-ile143thr (accessed [today's date]).

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