Is DSPP p.Leu48= (c.144A>G) pathogenic?

DSPP p.Leu48= (c.144A>G) is classified Benign/Likely benign in DSPP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-13). Low-frequency (popmax 1.05%, sas).

How common is DSPP p.Leu48= (c.144A>G) in the general population?

DSPP p.Leu48= (c.144A>G) is low-frequency (popmax 1.05%, sas) (gnomAD).

DSPP p.Leu48=

c.144A>G · rs187578466 · VCV741906

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.05%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.31	GERP -3.7
Overall
CADD	3.177	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.05% South Asian · 958/91,068 alleles

Filtering AF 0.997% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.974%

Overall 0.0678% 1,095/1,614,132 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.05%	95
Middle Eastern	0.148%	674
Remaining individualsnot grpmax-eligible	0.096%	1,042
Ashkenazi Jewishnot grpmax-eligible	0.0642%	1,558
Admixed American	0.01%	10,005
African / African-American	0.00533%	18,763
European (non-Finnish)	0.00331%	30,256

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.Leu48=
Coding: c.144A>G
dbSNP: rs187578466
Type: single nucleotide variant
Location: chr4:87612330 (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-leu48 (accessed [today's date]).

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