Is DEPDC1 p.Phe293Ser (c.878T>C) pathogenic?

DEPDC1 p.Phe293Ser (c.878T>C) is classified Uncertain significance in DEPDC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely pathogenic (0.6137); Very rare (popmax 0.00797%, nfe).

How common is DEPDC1 p.Phe293Ser (c.878T>C) in the general population?

DEPDC1 p.Phe293Ser (c.878T>C) is very rare (popmax 0.00797%, nfe) (gnomAD).

What do computational predictors say about DEPDC1 p.Phe293Ser (c.878T>C)?

AlphaMissense predicts likely pathogenic (score 0.6137) — an in-silico prediction, not a clinical call.

DEPDC1 p.Phe293Ser

c.878T>C · VCV4239631

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6137 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00797%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6137	likely pathogenic
REVEL	0.199	benign-leaning
SaProt	LLR -9.84	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 0.83, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 20 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	24.5	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 0.00797% European (non-Finnish) · 91/1,141,740 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00612%

Overall 0.00607% 94/1,547,688 alleles · very rare exomes 84/1,395,602 · genomes 10/152,086 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00797%	12,547
Remaining individualsnot grpmax-eligible	0.00334%	29,936
Admixed American	0.00198%	50,538

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: DEPDC1
Protein: p.Phe293Ser
Coding: c.878T>C
MANE Select: NM_001114120
Type: single nucleotide variant
Location: chr1:68483982 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.89 · 1 PDB
Residue 293: the rho-gap domain

Full DEPDC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DEPDC1 p.Ter812= Benign ★★ same type
DEPDC1 p.Ala175Val Uncertain significance ★ ⚠ same type
DEPDC1 p.Ala250Val Uncertain significance ★ ⚠ same type
DEPDC1 p.Ala280Thr Uncertain significance ★ ⚠ same type
DEPDC1 p.Ala377Thr Uncertain significance ★ ⚠ same type
DEPDC1 p.Ala46Ser Uncertain significance ★ same type
DEPDC1 p.Ala714Val Uncertain significance ★ ⚠ same type
DEPDC1 p.Arg105Ser 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/depdc1-p-phe293ser (accessed [today's date]).

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