Is DTHD1 p.Phe620fs (c.1860del) pathogenic?

DTHD1 p.Phe620fs (c.1860del) is classified Uncertain significance in DTHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-31). Ultra-rare (popmax 0.0333%, mid).

How common is DTHD1 p.Phe620fs (c.1860del) in the general population?

DTHD1 p.Phe620fs (c.1860del) is ultra-rare (popmax 0.0333%, mid) (gnomAD).

DTHD1 p.Phe620fs

c.1860del · rs1472500022 · VCV841261

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, mid)

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 7 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.7	phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0333% Middle Eastern · 2/5,998 alleles

Filtering AF 0.00588% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.000143% 2/1,399,994 alleles · ultra-rare

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: DTHD1
Protein: p.Phe620fs
Coding: c.1860del
MANE Select: NM_001170700
dbSNP: rs1472500022
Type: Deletion
Location: chr4:36308255 (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.Phe620Ser 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-phe620fs (accessed [today's date]).

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