Is DTHD1 p.Asp642= (c.1926C>T) pathogenic?

DTHD1 p.Asp642= (c.1926C>T) is classified Benign/Likely benign in DTHD1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-19). Rare (popmax 0.407%, afr).

How common is DTHD1 p.Asp642= (c.1926C>T) in the general population?

DTHD1 p.Asp642= (c.1926C>T) is rare (popmax 0.407%, afr) (gnomAD).

DTHD1 p.Asp642=

c.1926C>T · rs187161267 · VCV1165833

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.407%, afr)

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 0.36	phastCons 0.99
Overall
CADD	5.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.407% African / African-American · 298/73,174 alleles

Filtering AF 0.369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.354%

Overall 0.0212% 329/1,551,988 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.407%	246
Remaining individualsnot grpmax-eligible	0.0199%	5,016
Admixed American	0.0176%	5,667
European (non-Finnish)	0.000872%	114,705

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.Asp642=
Coding: c.1926C>T
MANE Select: NM_001170700
dbSNP: rs187161267
Type: single nucleotide variant
Location: chr4:36308324 (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-asp642 (accessed [today's date]).

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