Is DTHD1 p.Pro500fs (c.1499_1506del) pathogenic?

DTHD1 p.Pro500fs (c.14991506del) is classified Uncertain significance in DTHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-09). Absent from gnomAD.

How common is DTHD1 p.Pro500fs (c.1499_1506del) in the general population?

DTHD1 p.Pro500fs (c.1499_1506del) is absent from gnomAD (gnomAD).

DTHD1 p.Pro500fs

c.1499_1506del · rs2529730955 · VCV2041495

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 5 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.3	GERP 2.2, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DTHD1
Protein: p.Pro500fs
Coding: c.1499_1506del
MANE Select: NM_001170700
dbSNP: rs2529730955
Type: Deletion
Location: chr4:36294895 (GRCh38)
Gene constraint: LOEUF 1.034 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.99

Full DTHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DTHD1 p.Pro500Ser Uncertain significance ★ ⚠ same residue
DTHD1 p.Gln834_Ile836del Uncertain significance ★★ same type
DTHD1 p.Lys857fs Uncertain significance ★★ same type
DTHD1 p.Ser879fs Benign/Likely benign ★★ same type
DTHD1 p.Asn694fs Uncertain significance ★ same type
DTHD1 p.Asp582fs Uncertain significance ★ same type
DTHD1 p.Glu324fs Uncertain significance ★ same type
DTHD1 p.His849fs Uncertain significance ★ 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/dthd1-p-pro500fs (accessed [today's date]).

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