Is DSPP p.Ala50Pro (c.148G>C) pathogenic?

DSPP p.Ala50Pro (c.148G>C) is classified Likely benign in DSPP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-27). AlphaMissense: likely benign (0.2015); Rare (popmax 0.115%, afr).

How common is DSPP p.Ala50Pro (c.148G>C) in the general population?

DSPP p.Ala50Pro (c.148G>C) is rare (popmax 0.115%, afr) (gnomAD).

What do computational predictors say about DSPP p.Ala50Pro (c.148G>C)?

AlphaMissense predicts likely benign (score 0.2015) — an in-silico prediction, not a clinical call.

DSPP p.Ala50Pro

c.148G>C · rs376270964 · VCV1194811

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2015 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.115%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2015	likely benign
REVEL	0.356	indeterminate
SaProt	LLR -6.91	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 1.1	GERP -1.3, phastCons 0.01
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	18.44	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 0.115% African / African-American · 86/74,878 alleles

Filtering AF 0.0952% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.088%

Overall 0.00558% 90/1,613,918 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.115%	871
Remaining individualsnot grpmax-eligible	0.0048%	20,825
Admixed American	0.00167%	60,008

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.Ala50Pro
Coding: c.148G>C
dbSNP: rs376270964
Type: single nucleotide variant
Location: chr4:87612334 (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-ala50pro (accessed [today's date]).

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