Is DEPTOR p.Ile97Phe (c.289A>T) pathogenic?

DEPTOR p.Ile97Phe (c.289A>T) is classified Uncertain significance in DEPTOR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: likely pathogenic (0.6984); Very rare (popmax 0.00356%, nfe).

How common is DEPTOR p.Ile97Phe (c.289A>T) in the general population?

DEPTOR p.Ile97Phe (c.289A>T) is very rare (popmax 0.00356%, nfe) (gnomAD).

What do computational predictors say about DEPTOR p.Ile97Phe (c.289A>T)?

AlphaMissense predicts likely pathogenic (score 0.6984) — an in-silico prediction, not a clinical call.

DEPTOR p.Ile97Phe

c.289A>T · VCV3839540

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6984 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00356%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6984	likely pathogenic
REVEL	0.273	benign-leaning
SaProt	LLR -7.68	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 176 kb · p 0.55 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00356% European (non-Finnish) · 42/1,179,996 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.0026% 42/1,613,996 alleles · very rare

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: DEPTOR
Protein: p.Ile97Phe
Coding: c.289A>T
MANE Select: NM_022783
Type: single nucleotide variant
Location: chr8:119928566 (GRCh38)
Gene constraint: LOEUF 1.243 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.11 · 9 PDB
Residue 97: the dep 1 domain; a β-strand

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

Similar variants

DEPTOR p.Ala132Ser Uncertain significance ★ ⚠ same type
DEPTOR p.Ala132Val Uncertain significance ★ ⚠ same type
DEPTOR p.Ala337Val Uncertain significance ★ ⚠ same type
DEPTOR p.Ala363Thr Uncertain significance ★ ⚠ same type
DEPTOR p.Arg116His Uncertain significance ★ ⚠ same type
DEPTOR p.Arg163His Uncertain significance ★ same type
DEPTOR p.Arg222Gly Uncertain significance ★ ⚠ same type
DEPTOR p.Arg222Trp 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/deptor-p-ile97phe (accessed [today's date]).

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