Is DET1 p.Arg306Gln (c.917G>A) pathogenic?

DET1 p.Arg306Gln (c.917G>A) is classified Uncertain significance in DET1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-22). AlphaMissense: likely benign (0.0913); Ultra-rare (popmax 0.0483%, amr).

How common is DET1 p.Arg306Gln (c.917G>A) in the general population?

DET1 p.Arg306Gln (c.917G>A) is ultra-rare (popmax 0.0483%, amr) (gnomAD).

What do computational predictors say about DET1 p.Arg306Gln (c.917G>A)?

AlphaMissense predicts likely benign (score 0.0913) — an in-silico prediction, not a clinical call.

DET1 p.Arg306Gln

c.917G>A · VCV4239737

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0913 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0483%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0913	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -7.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 19 kb · p 0.99 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0483% Admixed American · 29/59,990 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0299%

Overall 0.00353% 57/1,613,748 alleles · ultra-rare exomes 52/1,461,590 · genomes 5/152,158 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0483%	2,069
Remaining individualsnot grpmax-eligible	0.0064%	15,616
European (non-Finnish)	0.00195%	51,297
South Asian	0.0011%	91,072

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.Arg306Gln
Coding: c.917G>A
MANE Select: NM_001144074
Type: single nucleotide variant
Location: chr15:88530789 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.29 · 12 PDB
Residue 306: an α-helix

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-arg306gln (accessed [today's date]).

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