Is DSPP p.Arg354Cys (c.1060C>T) pathogenic?

DSPP p.Arg354Cys (c.1060C>T) is classified Conflicting classifications of pathogenicity in DSPP (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.172); Rare (popmax 0.871%, sas); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Arg354Cys (c.1060C>T)?

DSPP p.Arg354Cys (c.1060C>T) is associated with Inborn genetic diseases, deafness, autosomal dominant 39, with dentinogenesis imperfecta 1 (ClinVar).

How common is DSPP p.Arg354Cys (c.1060C>T) in the general population?

DSPP p.Arg354Cys (c.1060C>T) is rare (popmax 0.871%, sas) (gnomAD).

What do computational predictors say about DSPP p.Arg354Cys (c.1060C>T)?

AlphaMissense predicts likely benign (score 0.172) — an in-silico prediction, not a clinical call.

DSPP p.Arg354Cys

c.1060C>T · rs61731011 · VCV260354

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.172 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.871%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.172	likely benign
REVEL	0.27	benign-leaning
SaProt	LLR -8.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.59	GERP -2.2, phastCons 0.003
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	17.43	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 0.871% South Asian · 793/91,060 alleles

Filtering AF 0.821% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.8%

Overall 0.497% 8,013/1,613,718 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.871%	115
European (non-Finnish)	0.536%	187
Middle Eastern	0.445%	225
Amishnot grpmax-eligible	0.439%	228
Remaining individualsnot grpmax-eligible	0.432%	232
Admixed American	0.383%	261
Finnishnot grpmax-eligible	0.327%	306
Ashkenazi Jewishnot grpmax-eligible	0.196%	510
East Asian	0.0824%	1,213
African / African-American	0.08%	1,250

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.Arg354Cys
Coding: c.1060C>T
dbSNP: rs61731011
Type: single nucleotide variant
Location: chr4:87613246 (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

Also linked: deafness, autosomal dominant 39, with dentinogenesis imperfecta 1

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-arg354cys (accessed [today's date]).

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