Is DTHD1 p.Arg793= (c.2379A>G) pathogenic?

DTHD1 p.Arg793= (c.2379A>G) is classified Benign/Likely benign in DTHD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-22). Ultra-rare (popmax 0.0334%, mid).

How common is DTHD1 p.Arg793= (c.2379A>G) in the general population?

DTHD1 p.Arg793= (c.2379A>G) is ultra-rare (popmax 0.0334%, mid) (gnomAD).

DTHD1 p.Arg793=

c.2379A>G · rs773475617 · VCV1170401

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.23	donor loss · deltas
Constraint at this position
Conservation	phyloP 4	GERP 2.1, phastCons 1
Overall
CADD	6.167	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% Middle Eastern · 2/5,994 alleles

Filtering AF 0.00588% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00415%

Overall 0.00594% 92/1,547,682 alleles · ultra-rare exomes 89/1,395,504 · genomes 3/152,178 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.158%	634
Middle Easterngrpmax	0.0334%	2,997
Remaining individualsnot grpmax-eligible	0.0133%	7,500
South Asian	0.0107%	9,307
African / African-American	0.00274%	36,453
European (non-Finnish)	0.00219%	45,765
Admixed American	0.00197%	50,772

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg793=
Coding: c.2379A>G
MANE Select: NM_001170700
dbSNP: rs773475617
Type: single nucleotide variant
Location: chr4:36339150 (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 c.1218+1G>A Uncertain significance ★★ same type
DTHD1 c.1219-2A>G Uncertain significance ★★ same type
DTHD1 p.Ala552Ser Uncertain significance ★★ ⚠ same type
DTHD1 p.Ala811Asp Uncertain significance ★★ ⚠ same type
DTHD1 p.Arg326Gln Uncertain significance ★★ ⚠ same type
DTHD1 p.Arg371Cys Uncertain significance ★★ ⚠ same type
DTHD1 p.Arg447Gln Uncertain significance ★★ ⚠ same type
DTHD1 p.Arg447Ter 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-arg793 (accessed [today's date]).

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