Is DET1 p.Phe528= (c.1584C>T) pathogenic?

DET1 p.Phe528= (c.1584C>T) is classified Likely benign in DET1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-28). Very rare (popmax 0.00445%, eas).

How common is DET1 p.Phe528= (c.1584C>T) in the general population?

DET1 p.Phe528= (c.1584C>T) is very rare (popmax 0.00445%, eas) (gnomAD).

DET1 p.Phe528=

c.1584C>T · VCV3271661

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

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 -0.027	GERP -4, phastCons 0.008
Overall
CADD	9.048	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00445% East Asian · 2/44,902 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00173% 28/1,613,942 alleles · very rare exomes 27/1,461,710 · genomes 1/152,232 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00445%	22,451
European (non-Finnish)	0.00203%	49,163
Admixed American	0.00167%	60,012
Remaining individualsnot grpmax-eligible	0.0016%	62,468

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: DET1
Protein: p.Phe528=
Coding: c.1584C>T
MANE Select: NM_001144074
Type: single nucleotide variant
Location: chr15:88513020 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.29 · 12 PDB
Residue 528: a β-strand

Full DET1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DET1 c.-1A>G Uncertain significance ★ same type
DET1 c.-3A>G Uncertain significance ★ same type
DET1 p.Ala134Val Uncertain significance ★ ⚠ same type
DET1 p.Ala160Pro Uncertain significance ★ ⚠ same type
DET1 p.Ala491Val Uncertain significance ★ ⚠ same type
DET1 p.Ala503Val Uncertain significance ★ ⚠ same type
DET1 p.Ala529Thr Uncertain significance ★ ⚠ same type
DET1 p.Ala93Gly 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/det1-p-phe528 (accessed [today's date]).

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