Is DSPP p.Leu60= (c.180G>T) pathogenic?

DSPP p.Leu60= (c.180G>T) is classified Benign/Likely benign in DSPP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.099%, mid).

How common is DSPP p.Leu60= (c.180G>T) in the general population?

DSPP p.Leu60= (c.180G>T) is ultra-rare (popmax 0.099%, mid) (gnomAD).

DSPP p.Leu60=

c.180G>T · rs200927888 · VCV715999

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.099%, mid)

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 -1.7	GERP -3.6
Overall
CADD	0.14	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.099% Middle Eastern · 6/6,062 alleles

Filtering AF 0.0925% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0906%

Overall 0.0789% 1,274/1,614,056 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.099%	1,010
European (non-Finnish)	0.0972%	1,029
Remaining individualsnot grpmax-eligible	0.0624%	1,603
Admixed American	0.06%	1,667
African / African-American	0.024%	4,168
South Asian	0.022%	4,554
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
Finnishnot grpmax-eligible	0.00781%	12,806

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.Leu60=
Coding: c.180G>T
dbSNP: rs200927888
Type: single nucleotide variant
Location: chr4:87612366 (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-leu60 (accessed [today's date]).

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