Is DLC1 p.Ser1007Arg (c.3021C>G) pathogenic?

DLC1 p.Ser1007Arg (c.3021C>G) is classified Uncertain significance in DLC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-10). AlphaMissense: likely pathogenic (0.9361); Ultra-rare (popmax 0.0233%, amr); Associated with colorectal cancer.

What condition is associated with DLC1 p.Ser1007Arg (c.3021C>G)?

DLC1 p.Ser1007Arg (c.3021C>G) is associated with colorectal cancer (ClinVar).

How common is DLC1 p.Ser1007Arg (c.3021C>G) in the general population?

DLC1 p.Ser1007Arg (c.3021C>G) is ultra-rare (popmax 0.0233%, amr) (gnomAD).

What do computational predictors say about DLC1 p.Ser1007Arg (c.3021C>G)?

AlphaMissense predicts likely pathogenic (score 0.9361) — an in-silico prediction, not a clinical call.

DLC1 p.Ser1007Arg

c.3021C>G · rs780462302 · VCV3082684

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9361 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

colorectal cancer

Computational evidence

Protein change
AlphaMissense	0.9361	likely pathogenic
REVEL	0.119	moderately benign-leaning
SaProt	LLR -6.23	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 0.84	GERP -0.05, phastCons 1
Overall
CADD	20.3	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 0.0233% Admixed American · 14/60,030 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.000958% 14/1,461,848 alleles · ultra-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: DLC1
Protein: p.Ser1007Arg
Coding: c.3021C>G
MANE Select: NM_003746 · reported on NM_182643
dbSNP: rs780462302
Type: single nucleotide variant
Location: chr8:13098545 (GRCh38)
Structure: AlphaFold pLDDT 95.45 · 22 PDB

Full DLC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

colorectal cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DLC1 c.2991-5C>A Uncertain significance ★★ same condition
DLC1 p.Ala1268Val Uncertain significance ★★ ⚠ same condition
DLC1 p.Ala350Val Uncertain significance ★★ ⚠ same condition
DLC1 p.Ala821Val Uncertain significance ★★ ⚠ same condition
DLC1 p.Arg1073Trp Uncertain significance ★★ ⚠ same condition
DLC1 p.Arg1126Cys Uncertain significance ★★ ⚠ same condition
DLC1 p.Arg1182Cys Uncertain significance ★★ ⚠ same condition
DLC1 p.Arg1182His Uncertain significance ★★ ⚠ same condition

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/dlc1-p-ser1007arg (accessed [today's date]).

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