Is DLC1 p.Pro206Ser (c.616C>T) pathogenic?

DLC1 p.Pro206Ser (c.616C>T) is classified Conflicting classifications of pathogenicity in DLC1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-31). AlphaMissense: likely benign (0.0706); Ultra-rare (popmax 0.029%, eas).

How common is DLC1 p.Pro206Ser (c.616C>T) in the general population?

DLC1 p.Pro206Ser (c.616C>T) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about DLC1 p.Pro206Ser (c.616C>T)?

AlphaMissense predicts likely benign (score 0.0706) — an in-silico prediction, not a clinical call.

DLC1 p.Pro206Ser

c.616C>T · rs556167966 · VCV2103800

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0706 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0706	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -5.23	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 -0.34	GERP -3.4
Overall
CADD	0.072	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 0.029% East Asian · 13/44,874 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00105% 17/1,613,974 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,452
Remaining individualsnot grpmax-eligible	0.0016%	62,500
European (non-Finnish)	0.000254%	393,332

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.Pro206Ser
Coding: c.616C>T
MANE Select: NM_003746 · reported on NM_182643
dbSNP: rs556167966
Type: single nucleotide variant
Location: chr8:13499456 (GRCh38)
Structure: AlphaFold pLDDT 95.45 · 22 PDB

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

Similar variants

DLC1 p.Pro206Leu Uncertain significance ★★ ⚠ same residue
DLC1 c.2991-5C>A Uncertain significance ★★ same type
DLC1 p.Ala1268Val Uncertain significance ★★ ⚠ same type
DLC1 p.Ala1278Thr Uncertain significance ★★ ⚠ same type
DLC1 p.Ala167Pro Uncertain significance ★★ ⚠ same type
DLC1 p.Ala350Val Uncertain significance ★★ ⚠ same type
DLC1 p.Ala752Gly Uncertain significance ★★ ⚠ same type
DLC1 p.Ala821Thr 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/dlc1-p-pro206ser (accessed [today's date]).

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