Is DTHD1 p.Phe894= (c.2682C>T) pathogenic?

DTHD1 p.Phe894= (c.2682C>T) is classified Likely benign in DTHD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-03). Very rare (popmax 0.00392%, amr).

How common is DTHD1 p.Phe894= (c.2682C>T) in the general population?

DTHD1 p.Phe894= (c.2682C>T) is very rare (popmax 0.00392%, amr) (gnomAD).

DTHD1 p.Phe894=

c.2682C>T · rs754727243 · VCV1119155

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00392%, amr)

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 2.9	GERP 2, phastCons 1
Overall
CADD	9.303	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00392% Admixed American · 2/50,966 alleles

Filtering AF 0.000651% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000243%

Overall 0.000322% 5/1,550,956 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00392%	25,483
Remaining individualsnot grpmax-eligible	0.00166%	60,072
European (non-Finnish)	0.000174%	573,388

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.Phe894=
Coding: c.2682C>T
MANE Select: NM_001170700
dbSNP: rs754727243
Type: single nucleotide variant
Location: chr4:36343785 (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.Phe894Tyr Uncertain significance ★★ ⚠ same residue
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

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-phe894 (accessed [today's date]).

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