Is DEPDC1B p.Pro8Arg (c.23C>G) pathogenic?

DEPDC1B p.Pro8Arg (c.23C>G) is classified Uncertain significance in DEPDC1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). AlphaMissense: ambiguous (0.5036); Very rare (popmax 0.00136%, afr).

How common is DEPDC1B p.Pro8Arg (c.23C>G) in the general population?

DEPDC1B p.Pro8Arg (c.23C>G) is very rare (popmax 0.00136%, afr) (gnomAD).

What do computational predictors say about DEPDC1B p.Pro8Arg (c.23C>G)?

AlphaMissense predicts ambiguous (score 0.5036) — an in-silico prediction, not a clinical call.

DEPDC1B p.Pro8Arg

c.23C>G · VCV4659605

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5036 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5036	ambiguous
REVEL	0.235	benign-leaning
SaProt	LLR -7.75	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.5	GERP 4.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 102 kb · p 0.00074 · regional, not allelic
Overall
CADD	26.6	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 0.00136% African / African-American · 1/73,500 alleles

Overall 7.11e-05% 1/1,405,648 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: DEPDC1B
Protein: p.Pro8Arg
Coding: c.23C>G
MANE Select: NM_018369
Type: single nucleotide variant
Location: chr5:60700071 (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-pro8arg (accessed [today's date]).

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