Is DLC1 p.Arg235Gln (c.704G>A) pathogenic?

DLC1 p.Arg235Gln (c.704G>A) is classified Uncertain significance in DLC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-02). AlphaMissense: likely benign (0.106); Ultra-rare (popmax 0.0372%, nfe); Associated with DLC1-related disorder.

What condition is associated with DLC1 p.Arg235Gln (c.704G>A)?

DLC1 p.Arg235Gln (c.704G>A) is associated with DLC1-related disorder, colorectal cancer (ClinVar).

How common is DLC1 p.Arg235Gln (c.704G>A) in the general population?

DLC1 p.Arg235Gln (c.704G>A) is ultra-rare (popmax 0.0372%, nfe) (gnomAD).

What do computational predictors say about DLC1 p.Arg235Gln (c.704G>A)?

AlphaMissense predicts likely benign (score 0.106) — an in-silico prediction, not a clinical call.

DLC1 p.Arg235Gln

c.704G>A · rs140615088 · VCV2636112

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.106 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0372%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DLC1-related disorder

Computational evidence

Protein change
AlphaMissense	0.106	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -5.44	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 3.2	GERP 2.2, phastCons 1
Overall
CADD	21.6	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 0.0372% European (non-Finnish) · 439/1,180,006 alleles

Filtering AF 0.0343% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0332%

Overall 0.0284% 458/1,613,808 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0372%	2,688
Remaining individualsnot grpmax-eligible	0.0112%	8,925
Finnishnot grpmax-eligible	0.0109%	9,136
East Asian	0.00446%	22,446
African / African-American	0.00401%	24,951

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.Arg235Gln
Coding: c.704G>A
MANE Select: NM_003746 · reported on NM_182643
dbSNP: rs140615088
Type: single nucleotide variant
Location: chr8:13499368 (GRCh38)
Structure: AlphaFold pLDDT 95.45 · 22 PDB

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

Disease context

DLC1-related disorder

Also linked: colorectal cancer

Similar variants

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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-arg235gln (accessed [today's date]).

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