Is DSPP p.Ser301Arg (c.903T>G) pathogenic?

DSPP p.Ser301Arg (c.903T>G) is classified Likely benign in DSPP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-22). AlphaMissense: ambiguous (0.4697); Rare (popmax 0.244%, afr).

How common is DSPP p.Ser301Arg (c.903T>G) in the general population?

DSPP p.Ser301Arg (c.903T>G) is rare (popmax 0.244%, afr) (gnomAD).

What do computational predictors say about DSPP p.Ser301Arg (c.903T>G)?

AlphaMissense predicts ambiguous (score 0.4697) — an in-silico prediction, not a clinical call.

DSPP p.Ser301Arg

c.903T>G · rs199872819 · VCV1203610

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.4697 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.244%, afr)

Computational evidence

Protein change
AlphaMissense	0.4697	ambiguous
REVEL	0.449	indeterminate
SaProt	LLR -7.88	tolerated
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.14	GERP 0.094, phastCons 0.089
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	18.46	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 0.244% African / African-American · 183/75,002 alleles

Filtering AF 0.215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.204%

Overall 0.0134% 216/1,614,078 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.244%	410
Remaining individualsnot grpmax-eligible	0.0272%	3,677
Admixed American	0.025%	4,001
South Asian	0.0011%	91,072

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.Ser301Arg
Coding: c.903T>G
dbSNP: rs199872819
Type: single nucleotide variant
Location: chr4:87613089 (GRCh38)

Full DSPP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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-ser301arg (accessed [today's date]).

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