Is DEPTOR p.Phe246Ser (c.737T>C) pathogenic?

DEPTOR p.Phe246Ser (c.737T>C) is classified Uncertain significance in DEPTOR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely pathogenic (0.991); Ultra-rare (popmax 0.0147%, afr).

How common is DEPTOR p.Phe246Ser (c.737T>C) in the general population?

DEPTOR p.Phe246Ser (c.737T>C) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

What do computational predictors say about DEPTOR p.Phe246Ser (c.737T>C)?

AlphaMissense predicts likely pathogenic (score 0.991) — an in-silico prediction, not a clinical call.

DEPTOR p.Phe246Ser

c.737T>C · VCV4659627

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.991 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.991	likely pathogenic
REVEL	0.251	benign-leaning
SaProt	LLR -4.54	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 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 176 kb · p 0.55 · regional, not allelic
Overall
CADD	25.2	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 0.0147% African / African-American · 11/74,922 alleles

Filtering AF 0.00815% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.000744% 12/1,613,976 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,811
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Phe246Ser
Coding: c.737T>C
MANE Select: NM_022783
Type: single nucleotide variant
Location: chr8:120001657 (GRCh38)
Gene constraint: LOEUF 1.243 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.11 · 9 PDB

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-phe246ser (accessed [today's date]).

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