Is DEPDC1B p.Pro136Arg (c.407C>G) pathogenic?

DEPDC1B p.Pro136Arg (c.407C>G) is classified Uncertain significance in DEPDC1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-28). AlphaMissense: likely benign (0.0759); Absent from gnomAD v4.1.

How common is DEPDC1B p.Pro136Arg (c.407C>G) in the general population?

DEPDC1B p.Pro136Arg (c.407C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DEPDC1B p.Pro136Arg (c.407C>G)?

AlphaMissense predicts likely benign (score 0.0759) — an in-silico prediction, not a clinical call.

DEPDC1B p.Pro136Arg

c.407C>G · VCV4659607

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0759 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0759	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -6.87	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 3.7	GERP 1.8, phastCons 0.99
Regional constraint	o/e 0.87	unconstrained · MANE · 102 kb · p 0.00074 · regional, not allelic
Overall
CADD	18.31	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DEPDC1B
Protein: p.Pro136Arg
Coding: c.407C>G
MANE Select: NM_018369
Type: single nucleotide variant
Location: chr5:60647441 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.79

Full DEPDC1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DEPDC1B p.Ala180Thr Uncertain significance ★ ⚠ same type
DEPDC1B p.Ala308Ser Uncertain significance ★ ⚠ same type
DEPDC1B p.Ala453Glu Uncertain significance ★ ⚠ same type
DEPDC1B p.Ala454Val Uncertain significance ★ ⚠ same type
DEPDC1B p.Arg101His Uncertain significance ★ ⚠ same type
DEPDC1B p.Arg158His Uncertain significance ★ ⚠ same type
DEPDC1B p.Arg15Ser Uncertain significance ★ ⚠ same type
DEPDC1B p.Arg174Cys 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/depdc1b-p-pro136arg (accessed [today's date]).

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