Is DLC1 p.Ser733= (c.2199C>T) pathogenic?

DLC1 p.Ser733= (c.2199C>T) is classified Benign in DLC1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Low-frequency (popmax 3.45%, afr); Associated with colorectal cancer.

What condition is associated with DLC1 p.Ser733= (c.2199C>T)?

DLC1 p.Ser733= (c.2199C>T) is associated with colorectal cancer (ClinVar).

How common is DLC1 p.Ser733= (c.2199C>T) in the general population?

DLC1 p.Ser733= (c.2199C>T) is low-frequency (popmax 3.45%, afr) (gnomAD).

DLC1 p.Ser733=

c.2199C>T · rs34941980 · VCV781117

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.45%, afr)

Conditions

colorectal cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.26	GERP -0.054, phastCons 0.33
Overall
CADD	9.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.45% African / African-American · 2,589/75,054 alleles

Filtering AF 3.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.29%

Overall 0.183% 2,961/1,614,100 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.45%	29
Middle Eastern	0.264%	379
Admixed American	0.237%	423
Remaining individualsnot grpmax-eligible	0.229%	437
South Asian	0.0121%	8,280
European (non-Finnish)	0.00508%	19,667

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.Ser733=
Coding: c.2199C>T
MANE Select: NM_003746 · reported on NM_182643
dbSNP: rs34941980
Type: single nucleotide variant
Location: chr8:13100138 (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 p.Ser733Ile Uncertain significance ★ ⚠ same residue
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

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-ser733 (accessed [today's date]).

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