Is DEPDC4 p.Ala13Pro (c.37G>C) pathogenic?

DEPDC4 p.Ala13Pro (c.37G>C) is classified Uncertain significance in DEPDC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: ambiguous (0.3406); Absent from gnomAD v4.1.

How common is DEPDC4 p.Ala13Pro (c.37G>C) in the general population?

DEPDC4 p.Ala13Pro (c.37G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DEPDC4 p.Ala13Pro (c.37G>C)?

AlphaMissense predicts ambiguous (score 0.3406) — an in-silico prediction, not a clinical call.

DEPDC4 p.Ala13Pro

c.37G>C · rs2096277389 · VCV3081742

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3406 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3406	ambiguous · top 10% in DEPDC4
REVEL	0.212	benign-leaning
SaProt	LLR -7.19	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 0.8	GERP 1.6, phastCons 0.007
Regional constraint	o/e 0.97	unconstrained · MANE · 25 kb · p 0.47 · regional, not allelic
Overall
CADD	20.7	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

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: DEPDC4
Protein: p.Ala13Pro
Coding: c.37G>C
MANE Select: NM_001364818
dbSNP: rs2096277389
Type: single nucleotide variant
Location: chr12:100267040 (GRCh38)
Gene constraint: LOEUF 1.415 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.58

Full DEPDC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DEPDC4 p.Ala13Glu Uncertain significance ★ ⚠ same residue
DEPDC4 p.Ala196Val Uncertain significance ★ ⚠ same type
DEPDC4 p.Ala8Pro Uncertain significance ★ ⚠ same type
DEPDC4 p.Asn255Asp Uncertain significance ★ ⚠ same type
DEPDC4 p.Asp65Ala Uncertain significance ★ ⚠ same type
DEPDC4 p.Cys124Phe Uncertain significance ★ ⚠ same type
DEPDC4 p.Gln125His Uncertain significance ★ ⚠ same type
DEPDC4 p.Gln246Arg 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/depdc4-p-ala13pro (accessed [today's date]).

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