Is DEPDC5 p.Arg78Trp (c.232C>T) pathogenic?

DEPDC5 p.Arg78Trp (c.232C>T) is classified Uncertain significance in DEPDC5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-12-18). AlphaMissense: likely pathogenic (0.6395); Very rare (popmax 0.00267%, afr).

How common is DEPDC5 p.Arg78Trp (c.232C>T) in the general population?

DEPDC5 p.Arg78Trp (c.232C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about DEPDC5 p.Arg78Trp (c.232C>T)?

AlphaMissense predicts likely pathogenic (score 0.6395) — an in-silico prediction, not a clinical call.

DEPDC5 p.Arg78Trp

c.232C>T · rs202233627 · VCV2664557

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6395 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6395	likely pathogenic
REVEL	0.208	benign-leaning
SaProt	LLR -12.07	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 64 kb · p 1.2e-06 · 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 0.00267% African / African-American · 2/74,910 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00062% 10/1,613,884 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,455
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)	0.000593%	168,561

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: DEPDC5
Protein: p.Arg78Trp
Coding: c.232C>T
MANE Select: NM_001242896
dbSNP: rs202233627
Type: single nucleotide variant
Location: chr22:31765013 (GRCh38)
Gene constraint: LOEUF 0.403 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.22 · 11 PDB

Full DEPDC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DEPDC5 p.Arg78Gln Uncertain significance ★ ⚠ same residue
DEPDC5 p.Arg78Leu Uncertain significance ★ ⚠ same residue
DEPDC5 p.Arg78Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
DEPDC5 p.Arg78_Leu79insTer Pathogenic ★ same residue
DEPDC5 p.Arg78fs Pathogenic ★ same residue
DEPDC5 c.1217+1G>A Likely pathogenic ★★ same type
DEPDC5 c.1218-1G>A Pathogenic ★★ same type
DEPDC5 c.1287+1G>A Pathogenic/Likely pathogenic ★★ 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/depdc5-p-arg78trp (accessed [today's date]).

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