Is DEPDC4 p.Pro3Ser (c.7C>T) pathogenic?

DEPDC4 p.Pro3Ser (c.7C>T) is classified Uncertain significance in DEPDC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-06). AlphaMissense: likely benign (0.0951); Very rare (popmax 0.00534%, afr).

How common is DEPDC4 p.Pro3Ser (c.7C>T) in the general population?

DEPDC4 p.Pro3Ser (c.7C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about DEPDC4 p.Pro3Ser (c.7C>T)?

AlphaMissense predicts likely benign (score 0.0951) — an in-silico prediction, not a clinical call.

DEPDC4 p.Pro3Ser

c.7C>T · VCV4010973

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0951 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0951	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -5.78	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 -0.15	GERP 0.39
Regional constraint	o/e 0.97	unconstrained · MANE · 25 kb · p 0.47 · regional, not allelic
Overall
CADD	14.09	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

Grpmax group 0.00534% African / African-American · 4/74,928 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00242% 39/1,612,954 alleles · very rare exomes 35/1,460,758 · genomes 4/152,196 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,732
Remaining individualsnot grpmax-eligible	0.0032%	31,227
European (non-Finnish)	0.0028%	35,744

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: DEPDC4
Protein: p.Pro3Ser
Coding: c.7C>T
MANE Select: NM_001364818
Type: single nucleotide variant
Location: chr12:100267070 (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 type
DEPDC4 p.Ala13Pro Uncertain significance ★ ⚠ same type
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

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-pro3ser (accessed [today's date]).

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