Is DPYS p.Glu507fs (c.1515_1518del) pathogenic?

DPYS p.Glu507fs (c.15151518del) is classified Conflicting classifications of pathogenicity in DPYS (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-23). Rare (popmax 0.37%, afr).

How common is DPYS p.Glu507fs (c.1515_1518del) in the general population?

DPYS p.Glu507fs (c.1515_1518del) is rare (popmax 0.37%, afr) (gnomAD).

DPYS p.Glu507fs

c.1515_1518del · rs538231044 · VCV728575

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.37%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2	GERP -2.6, phastCons 0.97
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.37% African / African-American · 278/75,044 alleles

Filtering AF 0.335% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.321%

Overall 0.0198% 320/1,614,146 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.37%	270
Remaining individualsnot grpmax-eligible	0.0224%	4,465
Admixed American	0.0217%	4,617
European (non-Finnish)	0.00127%	78,668

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: DPYS
Protein: p.Glu507fs
Coding: c.1515_1518del
MANE Select: NM_001385
dbSNP: rs538231044
Type: Deletion
Location: chr8:104381240 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.00 · 1 PDB

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

Similar variants

DPYS c.1092+5del Likely pathogenic ★★ same type
DPYS p.Ala34fs Pathogenic/Likely pathogenic ★★ same type
DPYS p.His419fs Likely pathogenic ★ same type
DPYS p.Lys159fs Pathogenic ★ same type
DPYS c.*166_*169del Uncertain significance ★ same type
DPYS p.Arg503fs Conflicting classifications of pathogenicity ★ same type
DPYS c.1443+15del Likely benign ★ same type
DPYS c.423+20del Likely benign ★ same type

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/dpys-p-glu507fs (accessed [today's date]).

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