Is DTX4 p.Thr284= (c.852C>T) pathogenic?

DTX4 p.Thr284= (c.852C>T) is classified Benign in DTX4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-04-26). Common (popmax 7.29%, afr) — too common for a highly-penetrant pathogenic allele.

DTX4 p.Thr284=

Q: How common is DTX4 p.Thr284= (c.852C>T) in the general population?

DTX4 p.Thr284= (c.852C>T) is common (popmax 7.29%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.852C>T · rs75403375 · VCV787910

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 7.29%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -2.6
Overall
CADD	0.347	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.29% African / African-American · 5,472/75,018 alleles

Filtering AF 7.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.07%

Overall 0.387% 6,243/1,613,724 alleles · common exomes 3,096/1,461,426 · genomes 3,147/152,298 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.29%	14
Remaining individualsnot grpmax-eligible	0.547%	183
Admixed American	0.493%	203
Middle Eastern	0.28%	357
South Asian	0.022%	4,553
European (non-Finnish)	0.00814%	12,290

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: DTX4
Protein: p.Thr284=
Coding: c.852C>T
MANE Select: NM_015177
dbSNP: rs75403375
Type: single nucleotide variant
Location: chr11:59182379 (GRCh38)
Gene constraint: LOEUF 0.732 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.83

Full DTX4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DTX4 p.Ala342= Benign ★★ same type
DTX4 p.Val257Gly Benign ★★ same type
DTX4 p.Val355= Benign ★★ same type
DTX4 p.Ala171Thr Uncertain significance ★ ⚠ same type
DTX4 p.Ala288Pro Uncertain significance ★ ⚠ same type
DTX4 p.Ala303Gly Uncertain significance ★ ⚠ same type
DTX4 p.Ala310Thr Uncertain significance ★ ⚠ same type
DTX4 p.Ala40Gly 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/dtx4-p-thr284 (accessed [today's date]).

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